BMJ 2000;321:405-412 ( 12 August )

Papers

Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study

Editorial by Tuomilehto

Irene M Stratton, senior statistician a, Amanda I Adler, epidemiologist a, H Andrew W Neil, university lecturer in clinical epidemiology b, David R Matthews, consultant diabetologist c, Susan E Manley, biochemist a, Carole A Cull, senior statistician a, David Hadden, consultant physician d, Robert C Turner, director e, Rury R Holman, director a,  on behalf of the UK Prospective Diabetes Study Group.

a Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, b Division of Public Health and Primary Care, Institute of Health Sciences, University of Oxford, Oxford OX3 7LF, c Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Radcliffe Infirmary, d Royal Victoria Hospital, Belfast BT12 6BA, e Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Radcliffe Infirmary

Correspondence to: I M Stratton irene.stratton{at}dtu.ox.ac.uk

    Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
Summary
References

Objective: To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.
Design: Prospective observational study.
Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland.
Participants: 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk.
Outcome measures: Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA1c adjusted for possible confounders at diagnosis of diabetes.
Results: The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA1c was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No threshold of risk was observed for any end point.
Conclusions: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA1c is likely to reduce the risk of complications, with the lowest risk being in those with HbA1c values in the normal range (<6.0%).

    Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
Summary
References

The UK prospective diabetes study (UKPDS), a clinical trial of a policy of intensive control of blood glucose after diagnosis of type 2 diabetes, which achieved a median haemoglobin A1c (HbA1c) of 7.0% compared with 7.9% in those allocated to conventional treatment over a median 10.0 years of follow up, has shown a substantial reduction in the risk of microvascular complications, with a reduction in the risk of myocardial infarction of borderline significance.1 Complementary information for estimates of the risk of complications at different levels of glycaemia can be obtained from observational analyses of data during the study.

In patients with type 2 diabetes previous prospective studies have shown an association between the degree of hyperglycaemia and increased risk of microvascular complications, 2 3 sensory neuropathy, 3 4 myocardial infarction, 2 5 6 stroke,7 macrovascular mortality,8-10 and all cause mortality. 9 11-14 Generally, these studies measured glycaemia as being high or low or assessed glycaemia on a single occasion, whereas repeated measurements of glycaemia over several years would be more informative.

The existence of thresholds of glycaemia---that is, concentrations above which the risk of complications markedly increases---has not been studied often in patients with type 2 diabetes. The relative risk for myocardial infarction seems to increase with any increase in glycaemia above the normal range, 15 16 whereas the risk for microvascular disease is thought to occur only with more extreme concentrations of glycaemia.17-19 The diabetes control and complications trial (DCCT) research group showed an association between glycaemia and the progression of microvascular complications in patients with type 1 diabetes for haemoglobin A1c over the range of 6-11% after a mean of six years of follow up.20 No specific thresholds of glycaemia were identified above which patients were at greater risk of progression of retinopathy, increased urinary albumin excretion, or nephropathy.19-21 Nor has any threshold of fasting plasma glucose concentration been identified for cardiovascular deaths. 22 23

We evaluated the relation between exposure to glycaemia over time and the development of macrovascular and microvascular complications and compared this with the results of the UKPDS trial of a policy of intensive control of blood glucose control.1

    Methods
Top
Abstract
Introduction
Methods
Results
Discussion
Summary
References

Participants recruited to the UKPDS
Details are presented in the companion paper (UKPDS 36) published in this issue (see page 412).

Participants in observational analysis
Of 5102 patients, 4585 white, Asian Indian, and Afro-Caribbean patients who had haemoglobin A1c (HbA1c) measured three months after the diagnosis of diabetes were included in analyses of incidence rates. Of these, 3642 with complete data for potential confounders were included in analyses of relative risk. Complete data were required for all participants included in the multivariate observational analyses. For this reason there are fewer (3642) participants in these analyses than in the clinical trial, despite the inclusion of patients not randomised in the trial. Their characteristics are presented in table 1.


                              
View this table:
[in this window]
[in a new window]
 

Table 1. Characteristics of patients included in proportional hazards model measured after three month dietary run-in after diagnosis of diabetes and those included in UKPDS glucose control study.1 Figures are means (SD) unless stated otherwise

Participants in UKPDS blood glucose control study
After a three month dietary run-in period patients were stratified on the basis of fasting plasma glucose concentration and body weight. The 3867 patients who had fasting plasma glucose concentrations between 6.1 and 15.0 mmol/l and no symptoms of hyperglycaemia were randomised to a policy of conventional glucose control, primarily with diet, or to an intensive policy with sulphonylurea or insulin. 1 24-26 The aim in the group allocated to conventional control (n=1138) was to obtain fasting plasma glucose concentration <15 mmol/l, but if concentrations rose to >= 15 mmol/l or symptoms of hyperglycaemia developed patients were secondarily randomised to non-intensive use of these pharmacological treatments, with the aim of achieving fasting plasma glucose concentrations <15 mmol/l without symptoms. The aim in the group allocated to intensive control (n=2729) was to achieve fasting plasma glucose concentration <6 mmol/l, primarily with a single pharmacological treatment. Details of treatments and their effect on glucose control have been published elsewhere.1

Biochemical methods
Biochemical methods have been reported previously.27 Haemoglobin A1c was measured by high performance liquid chromatography (Biorad Diamat automated glycosylated haemoglobin analyser), the range for people without diabetes being 4.5% to 6.2%. 27 28 Baseline variables are quoted for measurements after the initial dietary run-in period.

Glycaemic exposure
Exposure to glycaemia was measured firstly at baseline as haemoglobin A1c concentration and secondly over time as an updated mean of annual measurements of haemoglobin A1c concentration, calculated for each individual from baseline to each year of follow up. For example, at one year the updated mean is the average of the baseline and one year values and at three years is the average of baseline, one year, two year, and three year values.

Clinical complications
The clinical end points and their definitions are shown in the box in the companion paper (UKPDS 36) published in this issue (see page 412).

Statistical analysis

Incidence rates by category of glycaemia
The unadjusted incidence rates were calculated by dividing the number of people with a given complication by the person years of follow up for the given complication within each category of updated mean haemoglobin A1c concentration and reported as events per 1000 years of follow up.29 The categories were defined (median values in parentheses) as: <6% (5.6%), 6-<7% (6.5%), 7-<8% (7.5%), 8-<9% (8.4%), 9-<10% (9.4%), and >= 10% (10.6%) over the range of updated mean haemoglobin A1c of 4.6-11.2% (1st-99th centile). Follow up time was calculated from the end of the initial period of dietary treatment to the first occurrence of that complication or loss to follow up, death from another cause, or to the end of the study on 30 September 1997 for those who did not have that complication. Hence, follow up time is equivalent to duration of diabetes. For myocardial infarction and stroke for participants who had a non-fatal followed by a fatal event, the time to the first event was used. The rates were therefore for single and not recurrent events. The median follow up time for all cause mortality was 10.4 years.

We calculated adjusted incidence rates for each category of updated mean haemoglobin A1c using a Poisson regression model adjusted for male sex, white ethnic group, age at diagnosis 50-54 years, and duration of diabetes 7.5-12.5 years and expressed in events per 1000 person years of follow up. These parameters were chosen to reflect the median age and duration of diabetes and the modal ethnic group and sex.

Hazard ratio and risk reduction
To assess potential associations between updated mean haemoglobin A1c and complications we used proportional hazards regression (Cox) models. Potential confounding risk factors included in all Cox models were sex, age, ethnic group, smoking (current/ever/never) at time of diagnosis of diabetes, and baseline high and low density lipoprotein cholesterol, triglyceride, presence of albuminuria (> 50 mg/l measured in a single morning urine sample) measured after three months' dietary treatment, and systolic blood pressure represented by the mean of measures at two and nine months after diagnosis. The hazard ratio was used to estimate the relative risk. At each event time, the updated mean haemoglobin A1c value for individuals with an event was compared with the updated value of those who had not had an event by that time. The updated mean value was included as a time dependent covariate to evaluate glucose exposure during follow up. 20 29 30 It was included as a categorical variable in the categories of glycaemia listed above, with the lowest category (<6%) as the reference category assigned a hazard ratio of 1.0 and with the highest category >= 9%. (This is reflected in the point estimates as shown in figures 3 and 4.) Separate models, with updated mean haemoglobin A1c as a continuous variable, were used to determine reduction in risk associated with a 1% reduction in haemoglobin A1c (see regression lines in figures 3 and 4). We evaluated the presence of thresholds by visual inspection. The 95% confidence intervals were calculated on the basis of the floating absolute risk.31 Log linear relations are reported by convention. 1 32 The risk reduction associated with a reduction of 1% updated mean haemoglobin A1c was calculated as 100% minus the reciprocal of the hazard ratio expressed as a percentage. The risk reduction from the continuous variable model associated with a 1% reduction in observed haemoglobin A1c was compared with the risk reduction seen in the UKPDS intervention trial of an intensive versus a conventional policy of blood glucose control, for which no adjustment for potential confounders was required as they were balanced by randomisation.1



View larger version (14K):
[in this window]
[in a new window]
  		Fig 1.   Incidence rate and 95% confidence intervals for any end point related to diabetes by category of updated mean haemoglobin A1c concentration, adjusted for age, sex, and ethnic group, expressed for white men aged 50-54 years at diagnosis and with mean duration of diabetes of 10 years

To assess whether the association between mean updated haemoglobin A1c and complications was independent of randomisation, separate models included mean updated haemoglobin A1c and randomisation to either intensive or conventional policy, as well as all potential confounders listed above. The model for all end points related to diabetes included 3005 individuals.



View larger version (18K):
[in this window]
[in a new window]
  		Fig 2.   Incidence rates and 95% confidence intervals for myocardial infarction and microvascular complications by category of updated mean haemoglobin A1c concentration, adjusted for age, sex, and ethnic group, expressed for white men aged 50-54 years at diagnosis and with mean duration of diabetes of 10 years

Statistical analyses were performed with SAS version 6.12.33

    Results
Top
Abstract
Introduction
Methods
Results
Discussion
Summary
References

The risk of each of the microvascular and macrovascular complications of type 2 diabetes and cataract extraction was strongly associated with hyperglycaemia as measured by updated mean haemoglobin A1c. The incidence rates for any end point related to diabetes, adjusted for age, sex, ethnic group, and duration of diabetes, increased with each higher category of updated mean haemoglobin A1c, with no evidence of a threshold and with a threefold increase over the range of updated mean haemoglobin A1c of <6% (median 5.6%) to >= 10% (median 10.6%) (figs 1 and 2). The unadjusted and adjusted incidence rates are shown in table 2. Figure 2 shows the adjusted incidence rates for myocardial infarction and microvascular end points. The increase in the incidence rate for microvascular end points was greater over the range of increasing glycaemia than was the increase in the incidence rate for myocardial infarction. Thus at near normal concentrations of updated mean haemoglobin A1c the risk of myocardial infarction was twice to three times that of a microvascular end point, whereas in the highest category of haemoglobin A1c concentration (>= 10%) the risks were of the same order.


                              
View this table:
[in this window]
[in a new window]
 

Table 2. Incidence of complications in patients with type 2 diabetes by category of updated mean haemoglobin A1c concentration (%). Rates per 1000 person years' follow up adjusted in Poisson regression model to white men aged 50 to 54 years at diagnosis of diabetes and followed up for 7.5 to <12.5 years, termed "10 years" (n=4585)

The estimated hazard ratios associated with different categories of updated mean haemoglobin A1c concentration, relative to the lowest category, are shown as log linear plots in figures 3 and 4. Mortality related to diabetes and all cause mortality were both strongly associated with glycaemia (P<0.0001). The risk of each of the complications evaluated rose with increasing updated mean haemoglobin A1c concentration both before and after adjustment for baseline variables including age, sex, ethnic group, lipid concentrations, blood pressure, smoking, and albuminuria. The decrease in risk for each 1% reduction in updated mean haemoglobin A1c concentration is shown in table 3 and figures 3 and 4. The glycaemia associated reduction in risk for microvascular end points and for amputation or death from peripheral vascular disease was greater (by 37% and 43% per 1% reduction in haemoglobin A1c concentration, respectively, each P<0.0001) than it was for myocardial infarction, stroke, and heart failure (by 14% (P<0.0001), 12% (P=0.035), and 16% (P=0.021) per 1% haemoglobin A1c, respectively) (fig 4). In models that included a variable for conventional control of blood glucose or intensive control with either sulphonylurea or insulin, updated mean haemoglobin A1c remained associated with all complications, although for stroke and heart failure, where the numbers of events were lower than in the previous analyses, these were no longer significant. In these models, treatment of blood glucose per se had no association with any complication beyond that of mean updated haemoglobin A1c.



View larger version (20K):
[in this window]
[in a new window]
  		Fig 3.   Hazard ratios, with 95% confidence intervals as floating absolute risks, as estimate of association between category of updated mean haemoglobin A1c concentration and any end point or deaths related to diabetes and all cause mortality. Reference category (hazard ratio 1.0) is haemoglobin A1c <6% with log linear scales. P value reflects contribution of glycaemia to multivariate model. Data adjusted for age at diagnosis of diabetes, sex, ethnic group, smoking, presence of albuminuria, systolic blood pressure, high and low density lipoprotein cholesterol, and triglycerides



View larger version (37K):
[in this window]
[in a new window]
  		Fig 4.   Hazard ratios, with 95% confidence intervals as floating absolute risks, as estimate of association between category of updated mean haemoglobin A1c concentration and myocardial infarction, stroke, microvascular end points, cataract extraction, lower extremity amputation or fatal peripheral vascular disease, and heart failure. Reference category (hazard ratio 1.0) is haemoglobin A1c <6% with log linear scales. P value reflects contribution of glycaemia to multivariate model. Data adjusted for age at diagnosis of diabetes, sex, ethnic group, smoking, presence of albuminuria, systolic blood pressure, high and low density lipoprotein cholesterol, and triglycerides


                              
View this table:
[in this window]
[in a new window]
 

Table 3. Observational analysis of relation between glycaemic exposure and complications of diabetes as estimated by decrease in risk for 1% reduction in haemoglobin A1c (HbA1c) concentration, measured at baseline and as updated mean, controlled for age at diagnosis of diabetes, sex, ethnic group, smoking, albuminuria, systolic blood pressure, high and low density lipoprotein cholesterol, and triglycerides (n=3642) compared with results of clinical trial of intensive v conventional glucose control policy (n=3867)1

There was no indication of a threshold for any complication below which risk no longer decreased nor a level above which risk no longer increased. The updated mean haemoglobin A1c showed steeper relations than did baseline haemoglobin A1c (table 3), and when both glycaemic variables were included in a model for all complications of diabetes only updated mean haemoglobin A1c reached significance (P<0.0001).

    Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
Summary
References

This observational analysis shows highly significant associations between the development of each of the complications of diabetes, including mortality, across the wide range of exposure to glycaemia that occurs in patients with type 2 diabetes. This association remained after adjustment for other known risk factors, including age at diagnosis, sex, ethnic group, systolic blood pressure, lipid concentrations, smoking, and albuminuria. Each 1% reduction in haemoglobin A1c was associated with a 37% decrease in risk for microvascular complications and a 21% decrease in the risk of any end point or death related to diabetes. The association with glycaemia was less steep for stroke and heart failure, for which blood pressure is a major contributing factor. 32 34 35 In patients within the lowest category of updated mean haemoglobin A1c the incidence of myocardial infarction was higher than that of microvascular disease.5 These results suggest that, in these people, the effect of hyperglycaemia itself may account for at least part of the excess cardiovascular risk observed in diabetic compared with non-diabetic people beyond that explained by the conventional risk factors of dyslipidaemia, hypertension, and smoking.36 The rate of increase of relative risk for microvascular disease with hyperglycaemia was greater than that for myocardial infarction, which emphasises the crucial role of hyperglycaemia in the aetiology of small vessel disease and may explain the greater rate of microvascular complications seen in populations with less satisfactory control of glycaemia.

Relation to trial data
This observational analysis provides an estimate of the reduction in risk that might be achieved by the therapeutic lowering of haemoglobin A1c by 1.0%, but it is important to realise that epidemiological associations cannot necessarily be transferred to clinical practice. Tissue damage from previous hyperglycaemia may not promptly be overcome, but the results are not inconsistent with those achieved by the policy of intensive glucose control in the clinical trial.1 This suggests that the reduction in glycaemia obtained over a median 10 years of follow up of the trial, comparing median haemoglobin A1c 7.0% with 7.9%, provided much of the benefit that could be expected from that degree of improved glycaemic control. Our results suggest that intensive treatment with sulphonylurea or insulin does not have an effect beyond that of lowering blood glucose concentration with respect to altering risk. The 16% risk reduction (P=0.052) in myocardial infarction in the clinical trial in the group allocated to a policy of intensive blood glucose control (associated with a 0.9% difference in haemoglobin A1c) was similar to the 14% risk reduction seen in the epidemiological analysis, which was associated with a 1% reduction in concentration of updated mean haemoglobin A1c. The UKPDS clinical trial evaluated a policy of intensive glucose control based primarily on single pharmacological treatments to enable evaluation of the individual treatments. Now that the UKPDS has shown that improved glucose control reduces the risk of complications and that the treaments used are safe in clinical practice, a larger reduction in haemoglobin A1c might be achieved by the earlier use of combination treatments or by the use of newer treatments, which could further reduce the risk of myocardial infarction.


What is already known on this topic

The risk of developing complications of diabetes increases with increasing concentrations of hyperglycaemia

Reduction of hyperglycaemia in these individuals reduces the risk of complications

What this study adds

There is a direct relation between the risk of complications of diabetes and glycaemia over time

No threshold of glycaemia was observed for a substantive change in risk for any of the clinical outcomes examined

The lower the glycaemia the lower the risk of complications

The rate of increase of risk for microvascular disease with hyperglycaemia is greater than that for macrovascular disease

The observational analysis extends the range of hyperglycaemia studied in the UKPDS by including participants who, throughout the study, had near normal glucose concentrations on dietary treatment alone and participants who could never be treated by dietary treatment alone.37 The UKPDS population was likely to be at lower risk of complications than other diabetic populations. Hence, the incidence rates we report are perhaps lower than might be observed in other diabetic populations as the cohort was newly diagnosed with diabetes, excluded old or ill patients, and contained a small proportion (6%) of participants with impaired fasting glycaemia.38 None the less, the decrease in relative risk is unlikely to be different from other diabetic populations.

Lack of thresholds
We observed no thresholds of glycaemia for any type of complication of diabetes. This suggests that there is no specific target value of haemoglobin A1c for which one should aim but that the nearer to normal the haemoglobin A1c concentration the better. In reality, it is difficult to obtain and maintain near normal concentrations of haemoglobin A1c in patients with type 2 diabetes, particularly in those with a high concentration of haemoglobin A1c at diagnosis of diabetes.37 Intensification of treatment by adding insulin to improve the relatively modest reduction in glycaemia achieved with oral hypoglycaemic treatments can be constrained by reluctance from patients and providers because, in part, of side effects such as hypoglycaemia or weight gain. These observational analyses, together with the results of the clinical trial, however, indicate that any improvement in a raised haemoglobin A1c concentration is likely to reduce the risk of diabetic complications.

The magnitude of the risk reduction associated with a 1% reduction in haemoglobin A1c concentration for myocardial infarction and microvascular disease (mostly retinopathy) was consistent with that observed in a cohort of patients from Wisconsin.2 As in this analysis, a stronger association with haemoglobin A1c concentration was observed for amputation than for ischaemic heart disease, possibly because glycaemia increases the risk of microvascular disease, neuropathy, and peripheral arterial disease, each of which increases the risk of amputation. 4 8 18 39-41 The estimated 14% decrease in all cause mortality per 1% reduction in haemoglobin A1c concentration was similar to that seen in other studies that have assessed glycaemia as haemoglobin A1c as a continuous variable (per 1% change) in multivariate proportional hazards models.9

    Summary
Top
Abstract
Introduction
Methods
Results
Discussion
Summary
References

Both the observational and clinical trial analyses of an intensive glucose control policy suggest that even a modest reduction in glycaemia has the potential to prevent deaths from complications related to diabetes as cardiovascular and cerebrovascular disease account for 50-60% of all mortality in this and other diabetic populations. 8 42-47 Individuals with very high concentrations of glycaemia would be most likely to benefit from reduction of glycaemia as they are particularly at risk from the complications of type 2 diabetes, but the data suggest that any improvement in glycaemic control across the diabetic range is likely to reduce the risk of diabetic complications.

    Acknowledgments

The cooperation of the patients and many NHS and non-NHS staff at the centres is much appreciated. We thank Mr Dick Jelfs for the measurement of haemoglobin A1c. Details of participating centres can be found on the BMJ 's website.

Contributors: IMS selected the methodology, carried out the statistical analyses, coordinated the writing of the paper, and participated in the interpretation of results. AIA assisted with the writing of the paper and interpretation of results. HAWN, DRM, and DH participated in interpretation and revision of the paper. SEM managed the biochemical aspects and participated in interpretation and revision of the paper. CAC participated in preparation of the database and interpretation and revision of the paper. RCT and RRH were the principal investigators, planned and designed the study, and participated in interpretation and revision of the paper. RCT was also responsible for the initial draft of the paper. RRH is guarantor.

    Footnotes

Professor Turner died unexpectedly after completing work on this paper

Funding: The major grants for this study were from the UK Medical Research Council, the British Diabetic Association, the UK Department of Health, The National Eye Institute and The National Institute of Digestive, Diabetes and Kidney Disease in the National Institutes of Health, United States, The British Heart Foundation, Novo Nordisk, Bayer, Bristol-Myers Squibb, Hoechst, Lilly, Lipha, and Farmitalia Carlo Erba. Details of other funding companies and agencies, the supervising committees, and all participating staff can be found on the BMJ's website.

Competing interests: AIA has received fees for speaking from Bristol-Myers Squibb, SmithKline Beecham, and Pfizer. IMS has received support for attending conferences from Zeneca and Hoechst and fees for speaking from Hoechst. CAC has received support for attending conferences from Bristol-Myers Squibb, Novo Nordisk, and Pfizer and fees for speaking from Bristol-Myers Squibb and Novo Nordisk. DRM has received fees for speaking from Bristol-Myers Squibb, Novo Nordisk, SmithKline Beecham, and Lilly and research funding from Lilly. SEM has received support for attending conferences from Bayer and Novo Nordisk. RRH has received fees for consulting from Bayer, Boehringer Mannheim, Bristol-Myers Squibb, Hoechst, Lilly, Novo Nordisk, Pfizer, and SmithKline Beecham; support for attending conferences from Bayer, Bristol-Myers Squibb, Hoechst, Lilly, Lipha, Novo Nordisk, and SmithKline Beecham; and research funding from Bayer, Bristol-Myers Squibb, Lilly, Lipha, and Novo Nordisk.

Details of participating centres, staff, and committees and additional funding agencies are on the BMJ's website.


    References
Top
Abstract
Introduction
Methods
Results
Discussion
Summary
References

1. UKPDS Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853[CrossRef][Medline].
2. Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care 1995; 18: 258-268[Abstract].
3. Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973 (part 1). Diabetes Care 1978; 1: 168-188.
4. Adler AI, Boyko EJ, Ahroni AJ, Stensel V, Forsberg RC, Smith DG. Risk factors for diabetic peripheral sensory neuropathy. Results of the Seattle prospective diabetic foot study. Diabetes Care 1997; 20: 1162-1167[Abstract].
5. UKPDS Group. Risk factors for coronary artery disease in non-insulin dependent diabetes (UKPDS 23). BMJ 1998; 316: 823-828[Abstract/Free Full Text].
6. Kuusisto J, Mykkänen L, Pyörälä K, Laakso M. NIDDM and its metabolic control predict coronary heart disease in elderly subjects. Diabetes 1994; 43: 960-967[Abstract].
7. Lehto S, Ronnemaa T, Pyörälä K, Laakso M. Predictors of stroke in middle-aged patients with non-insulin-dependent diabetes. Stroke 1996; 27: 63-68[Abstract/Free Full Text].
8. Standl E, Balletshofer B, Dahl B, Weichenhain B, Stiegler H, Hormann A, et al. Predictors of 10-year macrovascular and overall mortality in patients with NIDDM: the Munich general practitioner project. Diabetologia 1996; 39: 1540-1545[CrossRef][Medline].
9. Groeneveld Y, Petri H, Hermans J, Springer MP. Relationship between blood glucose level and mortality in type 2 diabetes mellitus: a systematic review. Diabet Med 1999; 116: 2-13.
10. Uusitupa MI, Niskanen LK, Siitonen O, Voutilainen E, Pyörälä K. Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Diabetologia 1993; 36: 1175-1184[CrossRef][Medline].
11. Wei M, Gaskill SP, Haffner SM, Stern MP. Effects of diabetes and level of glycaemia on all-cause and cardiovascular mortality. Diabetes Care 1998; 21: 1167-1172[Abstract].
12. Hanefeld M, Fischer S, Julius U, Schulze J, Schwanebeck U, Schmechel H, et al. Risk factors for myocardial infarction and death in newly detected NIDDM: the diabetes intervention study, 11-year follow-up. Diabetologia 1996; 39: 1577-1583[CrossRef][Medline].
13. Knuiman MW, Welborn TA, Whittall DE. An analysis of excess mortality rates for persons with non-insulin-dependent diabetes mellitus in Western Australia using the Cox proportional hazards regression model. Am J Epidemiol 1992; 135: 638-648[Abstract/Free Full Text].
14. Sasaki A, Uehara M, Horiuchi N, Hasegawa K. A long-term follow-up study of diabetic patients in Osaka, Japan: mortality and causes of death. Tohoku J Exp Med 1983; 141(suppl): 639-644.
15. Balkau B, Shipley M, Jarrett RJ, Pyorala K, Pyorala M, Forhan A, et al. High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. Diabetes Care 1998; 21: 360-367[Abstract].
16. Fuller JH, Shipley MJ, Rose G, Jarrett RJ, Keen H. Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study. BMJ 1983; 287: 867-870.
17. Jarrett RJ, Keen H. Hyperglycaemia and diabetes mellitus. Lancet 1976; ii: 1009-1012.
18. Pettitt DJ, Knowler WC, Lisse JR, Bennett PH. Development of retinopathy and proteinuria in relation to plasma glucose concentration in Pima Indians. Lancet 1980; ii: 1050-1052.
19. Krolewski AS, Laffel LM, Krolewski M, Quinn M, Warram JH. Glycosylated hemoglobin and the risk of microalbuminuria in patients with insulin-dependent diabetes mellitus. N Engl J Med 1995; 332: 1251-1255[Abstract/Free Full Text].
20. DCCT Research Group. The absence of a glycemic threshold for the development of long-term complications: the perspective of the diabetes control and complications trial. Diabetes 1996; 45: 1289-1298[Abstract].
21. Orchard T, Forrest K, Ellis D, Becker D. Cumulative glycemic exposure and microvascular complications in insulin-dependent diabetes mellitus. Arch Intern Med 1997; 157: 1851-1856[Abstract/Free Full Text].
22. Balkau B, Bertrais S, Ducimitière P, Eschwège E. Is there a glycemic threshold for mortality risk? Diabetes Care 1999; 22: 696-699[Abstract/Free Full Text].
23. Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events: a metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 1999; 22: 233-240[Abstract/Free Full Text].
24. UKPDS Group. UK prospective diabetes study VIII: study design, progress and performance. Diabetologia 1991; 34: 877-890[CrossRef][Medline].
25. Manley SE, Cull CA, Holman RR. Relation of fasting plasma glucose on patients with type 2 diabetes in UKPDS randomised to and treated with diet or oral agents. Diabetes 2000; 49(suppl 1): A180.
26. UKPDS Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-865[CrossRef][Medline].
27. UKPDS Group. UK prospective diabetes study XI: biochemical risk factors in type 2 diabetic patients at diagnosis compared with age-matched normal subjects. Diabet Med 1994; 11: 534-544[Medline].
28. Cull CA, Manley SE, Stratton IM, Neil HAW, Ross IS, Holman RR, et al. Approach to maintaining comparability of biochemical data during long-term clinical trials. Clin Chem 1997; 43: 1913-1918[Abstract/Free Full Text].
29. Breslow NE, Day NE. The design and analysis of cohort studies. Statistical methods in cancer research II. Oxford: Oxford University Press, 1987.
30. Agresti A. Categorical data analysis. New York: Wiley, 1990.
31. Easton DF, Peto J, Babiker AG. Floating absolute risk: an alternative to relative risk in survival and case-control analysis avoiding an arbitrary reference group. Stat Med 1991; 10: 1025-1035[Medline].
32. UKPDS Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS 38). BMJ 1998; 317: 703-713[Abstract/Free Full Text].
33. SAS. Version 6. Cary, North Carolina: SAS Institute, 1990.
34. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al. Blood pressure, stroke, and coronary heart disease. Part 1: prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335: 765-774[CrossRef][Medline].
35. Adler AI, Stratton IM, Neil HAW, Yudkin JS, Matthews DR, Cull CA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000; 321: 412-419[Abstract/Free Full Text].
36. Stamler J. Epidemiology, established major risk factors and the primary prevention of coronary heart disease. In: Parmley WW, Chatterjee K, eds. Cardiology. Philadelphia: JB Lippincott, 1987:1-41.
37. UKPDS Group. UK prospective diabetes study 24: relative efficacy of sulfonylurea, insulin and metformin therapy in newly diagnosed non-insulin dependent diabetes with primary diet failure followed for six years. Ann Intern Med 1998; 128: 165-175[Abstract/Free Full Text].
38. American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1998; 21(suppl 1): 5-19.
39. Franklin GF, Shetterly SM, Cohen JA, Baxter J, Hamman RF. Risk factors for distal symmetric neuropathy in NIDDM. The San Luis Valley diabetes study. Diabetes Care 1994:1172-7.
40. Harris M, Eastman R, Cowie C. Symptoms of sensory neuropathy in adults with NIDDM in the US population. Diabetes Care 1993; 16: 1446-1452[Abstract].
41. Adler AI, Boyko EJ, Ahroni JH, Smith DG. Lower extremity amputation in diabetes mellitus: the independent effects of peripheral vascular disease, sensory neuropathy and foot ulcers. Diabetes Care 1999; 22: 1029-1035[Abstract/Free Full Text].
42. Adler AI, Matthews D, Holman RR, Turner RC. Type 2 diabetes and death: causes, estimated life expectancy and mortality rates---the UK prospective diabetes study. Diabetes 1998; 47(suppl 1): A71.
43. Palumbo PJ, Elveback LR, Chu CP, Connolly DC, Kurland LT. Diabetes mellitus: incidence, prevalence, survivorship and causes of death in Rochester, Minnesota, 1945-1970. Diabetes 1976; 25: 566-573[Abstract].
44. Panzram G. Mortality and survival in type 2 (non-insulin-dependent) diabetes mellitus. Diabetelogia 1987; 30: 123-131[CrossRef][Medline].
45. Goodkin G. Mortality in diabetes. A 20 year mortality study. J Occup Med 1975; 17: 716-721[Medline].
46. Wetterhall SF, Olson DR, DeStefano F, Stevenson JM, Ford ES, German RR, et al. Trends in diabetes and diabetic complications, 1980-1987. Diabetes Care 1992; 15: 960-967[Abstract].
47. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12 year cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care 1993; 16: 434-444[Abstract].

(Accepted 20 March 2000)

© BMJ 2000
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to StumbleUpon StumbleUpon   Add to Technorati Technorati    What's this?

Relevant Articles

Efficacy of self monitoring of blood glucose in patients with newly diagnosed type 2 diabetes (ESMON study): randomised controlled trial
Maurice J O’Kane, Brendan Bunting, Margaret Copeland, Vivien E Coates on behalf of the ESMON study group
BMJ 2008 336: 1174-1177. [Abstract] [Full Text] [PDF]

May be high risk, low benefit
John S Yudkin
BMJ 2008 336: 683. [Extract] [Full Text] [PDF]

Metformin, heart failure, and lactic acidosis: is metformin absolutely contraindicated?
A A Tahrani, G I Varughese, J H Scarpello, and F W F Hanna
BMJ 2007 335: 508-512. [Extract] [Full Text] [PDF]

Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review
Dean T Eurich, Finlay A McAlister, David F Blackburn, Sumit R Majumdar, Ross T Tsuyuki, Janice Varney, and Jeffrey A Johnson
BMJ 2007 335: 497. [Abstract] [Full Text] [PDF]

Management of hyperglycaemia in type 2 diabetes: the end of recurrent failure?
R J Heine, M Diamant, J-C Mbanya, and D M Nathan
BMJ 2006 333: 1200-1204. [Extract] [Full Text] [PDF]

Metabolic syndrome
Kamlesh Khunti and Melanie Davies
BMJ 2005 331: 1153-1154. [Extract] [Full Text] [PDF]

Glycaemia and vascular effects of type 2 diabetes
Brian Budenholzer, J K Cruickshank, R J Jarrett, Irene M Stratton, Carole A Cull, Susan E Manley, Amanda I Adler, H Andrew W Neil, David R Matthews, and Rury R Holman
BMJ 2001 322: 1245. [Extract] [Full Text]

People with type 2 diabetes should aim at normal blood pressure and HbA1c
BMJ 2000 321: 0. [Full Text]

Controlling glucose and blood pressure in type 2 diabetes
Jaakko Tuomilehto
BMJ 2000 321: 394-395. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

  • Gadsby, R. (2009). Treatment of type 2 diabetes. InnovAiT 2: 702-707 [Abstract] [Full text]  
  • Reaven, P. D., Moritz, T. E., Schwenke, D. C., Anderson, R. J., Criqui, M., Detrano, R., Emanuele, N., Kayshap, M., Marks, J., Mudaliar, S., Harsha Rao, R., Shah, J. H., Goldman, S., Reda, D. J., McCarren, M., Abraira, C., Duckworth, W., for the Veterans Affairs Diabetes Trial, (2009). Intensive Glucose-Lowering Therapy Reduces Cardiovascular Disease Events in Veterans Affairs Diabetes Trial Participants With Lower Calcified Coronary Atherosclerosis. Diabetes 58: 2642-2648 [Abstract] [Full text]  
  • Fonseca, V. A. (2009). Defining and Characterizing the Progression of Type 2 Diabetes. Diabetes Care 32: S151-S156 [Full text]  
  • Boutati, E. I., Raptis, S. A. (2009). Self-Monitoring of Blood Glucose as Part of the Integral Care of Type 2 Diabetes. Diabetes Care 32: S205-S210 [Abstract] [Full text]  
  • Swinnen, S. G., Hoekstra, J. B., DeVries, J. H. (2009). Insulin Therapy for Type 2 Diabetes. Diabetes Care 32: S253-S259 [Full text]  
  • Bretzel, R. G., Eckhard, M., Landgraf, W., Owens, D. R., Linn, T. (2009). Initiating Insulin Therapy in Type 2 Diabetic Patients Failing on Oral Hypoglycemic Agents: Basal or prandial insulin? The APOLLO trial and beyond. Diabetes Care 32: S260-S265 [Full text]  
  • Chiasson, J.-L. (2009). Early Insulin Use in Type 2 Diabetes: What are the cons?. Diabetes Care 32: S270-S274 [Full text]  
  • Gallwitz, B. (2009). Implications of Postprandial Glucose and Weight Control in People With Type 2 Diabetes: Understanding and implementing the International Diabetes Federation guidelines. Diabetes Care 32: S322-S325 [Full text]  
  • Davidson, J. A., Parkin, C. G. (2009). Is Hyperglycemia a Causal Factor in Cardiovascular Disease?: Does proving this relationship really matter? Yes. Diabetes Care 32: S331-S333 [Full text]  
  • Bianchi, C., Miccoli, R., Daniele, G., Penno, G., Del Prato, S. (2009). Is There Evidence That Oral Hypoglycemic Agents Reduce Cardiovascular Morbidity/Mortality? Yes. Diabetes Care 32: S342-S348 [Full text]  
  • Hanefeld, M., Bornstein, S. R., Pistrosch, F. (2009). Shifting the Disease Management Paradigm From Glucose: What are the cons?. Diabetes Care 32: S353-S356 [Full text]  
  • Heller, S. R., on behalf of the ADVANCE Collaborative Group, (2009). A Summary of the ADVANCE Trial. Diabetes Care 32: S357-S361 [Full text]  
  • Bailey, C. J., Blonde, L., Del Prato, S., Leiter, L. A., Nesto, R., Global Partnership for Effective Diabetes Manageme, (2009). What are the practical implications for treating diabetes in light of recent evidence? Updated recommendations from the Global Partnership for Effective Diabetes Management. Diabetes and Vascular Disease Research 6: 283-287 [Abstract]  
  • Stading, J., Herrmann, J., Walters, R., Destache, C., Chock, A. (2009). Impact of Pharmacist Intervention on Diabetes Patients in an Ambulatory Setting. Diabetes Spectr. 22: 241-246 [Full text]  
  • Bloomgarden, Z. T. (2009). The 6th Annual World Congress on the Insulin Resistance Syndrome. Diabetes Care 32: e114-e121 [Full text]  
  • Shiesh, S.-C., Wiedmeyer, H.-M., Kao, J.-T., Vasikaran, S. D., Lopez, J. B., the Laboratory Management Committee for the Asian-, (2009). Proficiency Testing of Hb A1c: A 4-Year Experience in Taiwan and the Asian Pacific Region. Clin. Chem. 55: 1876-1880 [Abstract] [Full text]  
  • Flegel, K. (2009). Controlling the complications of diabetes: It's about the sugar. CMAJ 181: 357-357 [Full text]  
  • Flegel, K. (2009). La maitrise des complications du diabete: une question de sucre. CMAJ 181: E106-E107 [Full text]  
  • Kelly, T. N., Bazzano, L. A., Fonseca, V. A., Thethi, T. K., Reynolds, K., He, J. (2009). Systematic Review: Glucose Control and Cardiovascular Disease in Type 2 Diabetes. ANN INTERN MED 151: 394-403 [Abstract] [Full text]  
  • Cox, M. E., Edelman, D. (2009). Tests for Screening and Diagnosis of Type 2 Diabetes. Clin. Diabetes 27: 132-138 [Abstract] [Full text]  
  • Manders, R. J., Pennings, B., Beckers, C. P., Aipassa, T. I, van Loon, L. J. (2009). Prevalence of daily hyperglycemia in obese type 2 diabetic men compared with that in lean and obese normoglycemic men: effect of consumption of a sucrose-containing beverage. Am. J. Clin. Nutr. 90: 511-518 [Abstract] [Full text]  
  • DeFronzo, R. A., Hissa, M. N., Garber, A. J., Luiz Gross, J., Yuyan Duan, R., Ravichandran, S., Chen, R. S., for the Saxagliptin 014 Study Group, (2009). The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes With Metformin Alone. Diabetes Care 32: 1649-1655 [Abstract] [Full text]  
  • Lee, T.-G., Koh, B., Lee, S. (2009). Sasang Constitution as a Risk Factor for Diabetes Mellitus: A Cross-Sectional Study. Evid Based Complement Alternat Med 6: 99-103 [Abstract] [Full text]  
  • Abhary, S., Hewitt, A. W., Burdon, K. P., Craig, J. E. (2009). A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy. Diabetes 58: 2137-2147 [Abstract] [Full text]  
  • Liu, L., Nettleton, J. A, Bertoni, A. G, Bluemke, D. A, Lima, J. A, Szklo, M. (2009). Dietary pattern, the metabolic syndrome, and left ventricular mass and systolic function: the Multi-Ethnic Study of Atherosclerosis. Am. J. Clin. Nutr. 90: 362-368 [Abstract] [Full text]  
  • Narendran, P. (2009). Cardiovascular benefit of intensive glucose control: approaching closure. British Journal of Diabetes & Vascular Disease 9: 175-176 [Abstract]  
  • Baliga, V., Sapsford, R. (2009). Review article: Diabetes mellitus and heart failure -- an overview of epidemiology and management. Diabetes and Vascular Disease Research 6: 164-171 [Abstract]  
  • Hemmingsen, B., Lund, S. S, Wetterslev, J., Vaag, A. (2009). Oral hypoglycaemic agents, insulin resistance and cardiovascular disease in patients with type 2 diabetes. Eur J Endocrinol 161: 1-9 [Abstract] [Full text]  
  • Shea, S., Weinstock, R. S, Teresi, J. A, Palmas, W., Starren, J., Cimino, J. J, Lai, A. M, Field, L., Morin, P. C, Goland, R., Izquierdo, R. E, Ebner, S., Silver, S., Petkova, E., Kong, J., Eimicke, J. P, IDEATel Consortium, (2009). A Randomized Trial Comparing Telemedicine Case Management with Usual Care in Older, Ethnically Diverse, Medically Underserved Patients with Diabetes Mellitus: 5 Year Results of the IDEATel Study. J Am Med Inform Assoc 16: 446-456 [Abstract] [Full text]  
  • Shea, S., Weinstock, R. S., Teresi, J. A., Palmas, W., Starren, J., Cimino, J. J., Lai, A. M., Field, L., Morin, P. C., Goland, R., Izquierdo, R. E., Ebner, S., Silver, S., Petkova, E., Kong, J., Eimicke, J. P., IDEATel Consortium, (2009). A Randomized Trial Comparing Telemedicine Case Management with Usual Care in Older, Ethnically Diverse, Medically Underserved Patients with Diabetes Mellitus: 5 Year Results of the IDEATel Study. J. Am. Med. Inform. Assoc. 16: 446-456 [Abstract] [Full text]  
  • Vanschoonbeek, K., Lansink, M., van Laere, K. M. J., Senden, J. M. G., Verdijk, L. B., van Loon, L. J. C. (2009). Slowly Digestible Carbohydrate Sources Can Be Used to Attenuate the Postprandial Glycemic Response to the Ingestion of Diabetes-Specific Enteral Formulas. The Diabetes Educator 35: 631-640 [Abstract] [Full text]  
  • Badawi, O., Yeung, S. Y., Rosenfeld, B. A. (2009). Evaluation of Glycemic Control Metrics for Intensive Care Unit Populations. American Journal of Medical Quality 24: 310-320 [Abstract]  
  • O'Kane, M. J, Pickup, J. (2009). Self-monitoring of blood glucose in diabetes: is it worth it?. Ann Clin Biochem 46: 273-282 [Abstract] [Full text]  
  • The International Expert Committee, (2009). International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes. Diabetes Care 32: 1327-1334 [Full text]  
  • Clement, M., Bhattacharyya, O., Conway, J. R. (2009). Is tight glycemic control in type 2 diabetes really worthwhile?: YES. cfp 55: 580-582 [Full text]  
  • Clement, M., Bhattacharyya, O., Conway, J. R. (2009). Vaut-il vraiment la peine d'exercer un strict controle glycemique pour le diabete de type 2?: OUI. cfp 55: 584-588 [Full text]  
  • Pellitero, S., Reverter, J. L, Granada, M. L., Pizarro, E., Pastor, M C., Tassies, D., Reverter, J. C., Salinas, I., Sanmarti, A. (2009). Association of the IGF1/pregnancy-associated plasma protein-A system and adipocytokine levels with the presence and the morphology of carotid plaques in type 2 diabetes mellitus patients with stable glycaemic control. Eur J Endocrinol 160: 925-932 [Abstract] [Full text]  
  • Dale, A. C., Midthjell, K., Nilsen, T. I., Wiseth, R., Vatten, L. J. (2009). Glycaemic control in newly diagnosed diabetes patients and mortality from ischaemic heart disease: 20-year follow-up of the HUNT Study in Norway. Eur Heart J 30: 1372-1377 [Abstract] [Full text]  
  • Livesey, G. (2009). Fructose Ingestion: Dose-Dependent Responses in Health Research. J. Nutr. 139: 1246S-1252S [Abstract] [Full text]  
  • Williams, G. C., Patrick, H., Niemiec, C. P., Williams, L. K., Divine, G., Lafata, J. E., Heisler, M., Tunceli, K., Pladevall, M. (2009). Reducing the Health Risks of Diabetes: How Self-determination Theory May Help Improve Medication Adherence and Quality of Life. The Diabetes Educator 35: 484-492 [Abstract] [Full text]  
  • Ko, G. T.C., So, W.-Y., Tong, P. C., Chan, W.-B., Yang, X., Ma, R. C., Kong, A. P., Ozaki, R., Yeung, C.-Y., Chow, C.-C., Chan, J. C. (2009). Effect of interactions between C peptide levels and insulin treatment on clinical outcomes among patients with type 2 diabetes mellitus. CMAJ 180: 919-926 [Abstract] [Full text]  
  • Morrow, D. A., Scirica, B. M., Chaitman, B. R., McGuire, D. K., Murphy, S. A., Karwatowska-Prokopczuk, E., McCabe, C. H., Braunwald, E., for the MERLIN-TIMI 36 Investigators, (2009). Evaluation of the Glycometabolic Effects of Ranolazine in Patients With and Without Diabetes Mellitus in the MERLIN-TIMI 36 Randomized Controlled Trial. Circulation 119: 2032-2039 [Abstract] [Full text]  
  • Vivo, R. P., Krim, S. R., Cevik, C., Witteles, R. M. (2009). Heart failure in hispanics.. J Am Coll Cardiol 53: 1167-1175 [Abstract] [Full text]  
  • Oates, T.W., Dowell, S., Robinson, M., McMahan, C.A. (2009). Glycemic Control and Implant Stabilization in Type 2 Diabetes Mellitus. JDR 88: 367-371 [Abstract] [Full text]  
  • Leal, J., Gray, A. M., Clarke, P. M. (2009). Development of life-expectancy tables for people with type 2 diabetes. Eur Heart J 30: 834-839 [Abstract] [Full text]  
  • Nuzum, D. S., Merz, T. (2009). Macrovascular Complications of Diabetes Mellitus. Journal of Pharmacy Practice 22: 135-148 [Abstract]  
  • Goldberg, R. B., Temprosa, M., Haffner, S., Orchard, T. J., Ratner, R. E., Fowler, S. E., Mather, K., Marcovina, S., Saudek, C., Matulik, M. J., Price, D. (2009). Effect of Progression From Impaired Glucose Tolerance to Diabetes on Cardiovascular Risk Factors and Its Amelioration by Lifestyle and Metformin Intervention: The Diabetes Prevention Program randomized trial by the Diabetes Prevention Program Research Group. Diabetes Care 32: 726-732 [Abstract] [Full text]  
  • Arnold, J. M. O., Gilbert, R. E. (2009). Novel risk factors for heart failure when the whole may be greater than the sum of its parts.. J Am Coll Cardiol 53: 763-764 [Full text]  
  • Irwin, N., Moodley, M., Flatt, P. R (2009). Review: Maximising the therapeutic potential of glucagon-like peptide-1 in type 2 diabetes. British Journal of Diabetes & Vascular Disease 9: 44-52 [Abstract]  
  • Campbell, I. W (2009). Review: Durable glycaemia -- the promised land. British Journal of Diabetes & Vascular Disease 9: 53-63 [Abstract]  
  • Song, S. H, Gray, T. A (2009). Management of type 2 diabetes and lipids: a critique of the NICE guidelines 2008. British Journal of Diabetes & Vascular Disease 9: 69-74 [Abstract]  
  • Shahangian, S., Snyder, S. R. (2009). Laboratory Medicine Quality Indicators: A Review of the Literature. Am J Clin Pathol 131: 418-431 [Abstract] [Full text]  
  • Raz, I., Wilson, P. W.F., Strojek, K., Kowalska, I., Bozikov, V., Gitt, A. K., Jermendy, G., Campaigne, B. N., Kerr, L., Milicevic, Z., Jacober, S. J. (2009). Effects of Prandial Versus Fasting Glycemia on Cardiovascular Outcomes in Type 2 Diabetes: The HEART2D trial. Diabetes Care 32: 381-386 [Abstract] [Full text]  
  • Ceriello, A. (2009). Postprandial Hyperglycemia and Cardiovascular Disease: Is the HEART2D study the answer?. Diabetes Care 32: 521-522 [Full text]  
  • Gerstein, H. C. (2009). Dysglycemia and Cardiovascular Risk in the General Population. Circulation 119: 773-775 [Full text]  
  • Horton, E. S. (2009). Defining the role of basal and prandial insulin for optimal glycemic control.. J Am Coll Cardiol 53: S21-S27 [Abstract] [Full text]  
  • COLE, A., GILL, T. K., SHANAHAN, E. M., PHILLIPS, P., TAYLOR, A. W., HILL, C. L. (2009). Is Diabetes Associated with Shoulder Pain or Stiffness? Results from a Population Based Study. The Journal of Rheumatology 36: 371-377 [Abstract] [Full text]  
  • Havas, S. (2009). The ACCORD Trial and Control of Blood Glucose Level in Type 2 Diabetes Mellitus: Time to Challenge Conventional Wisdom. Arch Intern Med 169: 150-154 [Full text]  
  • Duckworth, W., Abraira, C., Moritz, T., Reda, D., Emanuele, N., Reaven, P. D., Zieve, F. J., Marks, J., Davis, S. N., Hayward, R., Warren, S. R., Goldman, S., McCarren, M., Vitek, M. E., Henderson, W. G., Huang, G. D., the VADT Investigators, (2009). Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. NEJM 360: 129-139 [Abstract] [Full text]  
  • Pound, N., Penton-Voak, I. S, Surridge, A. K (2009). Testosterone responses to competition in men are related to facial masculinity. Proc R Soc B 276: 153-159 [Abstract] [Full text]  
  • Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., Zinman, B. (2009). Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Clin. Diabetes 27: 4-16 [Full text]  
  • McGill, J. B. (2009). Reexamining Misconceptions About {beta}-Blockers in Patients With Diabetes. Clin. Diabetes 27: 36-46 [Abstract] [Full text]  
  • Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., Zinman, B. (2009). Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Spectr. 22: 6-17 [Full text]  
  • Bashan, N., Kovsan, J., Kachko, I., Ovadia, H., Rudich, A. (2009). Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species. Physiol. Rev. 89: 27-71 [Abstract] [Full text]  
  • Gulcelik, N. E., Karakaya, J., Gedik, A., Usman, A., Gurlek, A. (2009). Serum vaspin levels in type 2 diabetic women in relation to microvascular complications. Eur J Endocrinol 160: 65-70 [Abstract] [Full text]  
  • Anderson, R. T., Girman, C. J., Pawaskar, M. D., Camacho, F. T., Calles, J., Kelly, W. S., DeMuro, C., Balkrishnan, R. (2009). Diabetes Medication Satisfaction Tool: A focus on treatment regimens. Diabetes Care 32: 51-53 [Abstract] [Full text]  
  • West, N. A., Hamman, R. F., Mayer-Davis, E. J., D'Agostino, R. B. Jr., Marcovina, S. M., Liese, A. D., Zeitler, P. S., Daniels, S. R., Dabelea, D. (2009). Cardiovascular Risk Factors Among Youth With and Without Type 2 Diabetes: Differences and possible mechanisms. Diabetes Care 32: 175-180 [Abstract] [Full text]  
  • Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., Zinman, B. (2009). Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 32: 193-203 [Abstract] [Full text]  
  • Pratley, R. E. (2009). Expanding Treatment Options for Type 2 Diabetes: The Old and the New. The Diabetes Educator 35: 4S-11S [Abstract] [Full text]  
  • American Diabetes Association, (2009). Standards of Medical Care in Diabetes--2009. Diabetes Care 32: S13-S61 [Full text]  
  • Montori, V. M, Malaga, G. (2008). Intensive glucose control did not prevent important complications in type 2 diabetes. Evid. Based Med. 13: 168-169 [Full text]  
  • Matthews, J. E., Stewart, M. W., De Boever, E. H., Dobbins, R. L., Hodge, R. J., Walker, S. E., Holland, M. C., Bush, M. A., for the Albiglutide Study Group, (2008). Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Albiglutide, a Long-Acting Glucagon-Like Peptide-1 Mimetic, in Patients with Type 2 Diabetes. J. Clin. Endocrinol. Metab. 93: 4810-4817 [Abstract] [Full text]  
  • Anselmino, M., Wallander, M., Norhammar, A., Mellbin, L., Ryden, L. (2008). Implications of abnormal glucose metabolism in patients with coronary artery disease. Diabetes and Vascular Disease Research 5: 285-290 [Abstract]  
  • Livesey, G., Taylor, R. (2008). Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am. J. Clin. Nutr. 88: 1419-1437 [Abstract] [Full text]  
  • Gold, R., Yu, K., Liang, L.-J., Adler, F., Balingit, P., Luc, P., Hernandez, J., Toro, Y., Modilevsky, T. (2008). Synchronous Provider Visit and Self-management Education Improves Glycemic Control in Hispanic Patients With Long-Standing Type 2 Diabetes. The Diabetes Educator 34: 990-995 [Abstract] [Full text]  
  • Fonseca, V. A (2008). Defining and characterising the progression of type 2 diabetes. British Journal of Diabetes & Vascular Disease 8: S3-S9 [Abstract]  
  • Kilpatrick, E. S., Rigby, A. S., Atkin, S. L. (2008). A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes: Data from the Diabetes Control and Complications Trial. Diabetes Care 31: 2198-2202 [Abstract] [Full text]  
  • Giorda, C. B., Avogaro, A., Maggini, M., Lombardo, F., Mannucci, E., Turco, S., Alegiani, S. S., Raschetti, R., Velussi, M., Ferrannini, E., for the Diabetes and Informatics Study Group, (2008). Recurrence of Cardiovascular Events in Patients With Type 2 Diabetes: Epidemiology and risk factors. Diabetes Care 31: 2154-2159 [Abstract] [Full text]  
  • Esposito, K., Ciotola, M., Maiorino, M. I., Gualdiero, R., Schisano, B., Ceriello, A., Beneduce, F., Feola, G., Giugliano, D. (2008). Addition of Neutral Protamine Lispro Insulin or Insulin Glargine to Oral Type 2 Diabetes Regimens for Patients with Suboptimal Glycemic Control: A Randomized Trial. ANN INTERN MED 149: 531-539 [Abstract] [Full text]  
  • HOOGWERF, B. J. (2008). Does intensive therapy of type 2 diabetes help or harm? Seeking accord on ACCORD. Cleveland Clinic Journal of Medicine 75: 729-737 [Abstract] [Full text]  
  • Almeida, J. C., Zelmanovitz, T., Vaz, J. S., Steemburgo, T., Perassolo, M. S., Gross, J. L., Azevedo, M. J. (2008). Sources of Protein and Polyunsaturated Fatty Acids of the Diet and Microalbuminuria in Type 2 Diabetes Mellitus. J. Am. Coll. Nutr. 27: 528-537 [Abstract] [Full text]  
  • Feldstein, A. C., Nichols, G. A., Smith, D. H., Stevens, V. J., Bachman, K., Rosales, A. G., Perrin, N. (2008). Weight Change in Diabetes and Glycemic and Blood Pressure Control. Diabetes Care 31: 1960-1965 [Abstract] [Full text]  
  • Patasi, B., Conway, J. R. (2008). Enhancing diabetes care in family practice: A flow sheet. cfp 54: 1237-1238 [Full text]  
  • Nikkanen, T., Timonen, M., Ylitalo, K., Timonen, O., Keinanen-Kiukaanniemi, S., Rajala, U. (2008). Quality of diabetes care among patients managed by teleconsultation. J Telemed Telecare 14: 295-299 [Abstract] [Full text]  
  • Kilpatrick, E S (2008). Haemoglobin A1c in the diagnosis and monitoring of diabetes mellitus. J. Clin. Pathol. 61: 977-982 [Abstract] [Full text]  
  • Berg, A H, Sacks, D B (2008). Haemoglobin A1c analysis in the management of patients with diabetes: from chaos to harmony. J. Clin. Pathol. 61: 983-987 [Abstract] [Full text]  
  • Gerstein, H. C., Swedberg, K., Carlsson, J., McMurray, J. J. V., Michelson, E. L., Olofsson, B., Pfeffer, M. A., Yusuf, S., for the CHARM Program Investigators, (2008). The Hemoglobin A1c Level as a Progressive Risk Factor for Cardiovascular Death, Hospitalization for Heart Failure, or Death in Patients With Chronic Heart Failure: An Analysis of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program. Arch Intern Med 168: 1699-1704 [Abstract] [Full text]  
  • Wilper, A. P., Woolhandler, S., Lasser, K. E., McCormick, D., Bor, D. H., Himmelstein, D. U. (2008). A National Study of Chronic Disease Prevalence and Access to Care in Uninsured U.S. Adults. ANN INTERN MED 149: 170-176 [Abstract] [Full text]  
  • Bloomgarden, Z. T. (2008). Approaches to Treatment of Type 2 Diabetes. Diabetes Care 31: 1697-1703 [Full text]  
  • Fonseca, V. A., Rosenstock, J., Wang, A. C., Truitt, K. E., Jones, M. R. (2008). Colesevelam HCl Improves Glycemic Control and Reduces LDL Cholesterol in Patients With Inadequately Controlled Type 2 Diabetes on Sulfonylurea-Based Therapy. Diabetes Care 31: 1479-1484 [Abstract] [Full text]  
  • Goldberg, R. B., Fonseca, V. A., Truitt, K. E., Jones, M. R. (2008). Efficacy and Safety of Colesevelam in Patients With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Receiving Insulin-Based Therapy. Arch Intern Med 168: 1531-1540 [Abstract] [Full text]  
  • Macdonald, D. R, Hanson, A. M, Holland, M. R, Singh, B. M (2008). Clinical impact of variability in HbA1c as assessed by simultaneously measuring fructosamine and use of error grid analysis. Ann Clin Biochem 45: 421-425 [Abstract] [Full text]  
  • Dokken, B. B. (2008). The Pathophysiology of Cardiovascular Disease and Diabetes: Beyond Blood Pressure and Lipids. Diabetes Spectr. 21: 160-165 [Abstract] [Full text]  
  • Triplitt, C., Alvarez, C. A. (2008). Best Practices for Lowering the Risk of Cardiovascular Disease in Diabetes. Diabetes Spectr. 21: 177-189 [Abstract] [Full text]  
  • Ramser, K. L., Sprabery, L. R., George, C. M., Hamann, G. L., Vallejo, V. A., Dorko, C. S., Kuhl, D. A. (2008). Physician-Pharmacist Collaboration in the Management of Patients With Diabetes Resistant to Usual Care. Diabetes Spectr. 21: 209-214 [Full text]  
  • McAlister, F. A., Eurich, D. T., Majumdar, S. R., Johnson, J. A. (2008). The risk of heart failure in patients with type 2 diabetes treated with oral agent monotherapy. Eur J Heart Fail 10: 703-708 [Abstract] [Full text]  
  • Cefalu, W. T. (2008). Glycemic Targets and Cardiovascular Disease. NEJM 358: 2633-2635 [Full text]  

Rapid Responses:

Read all Rapid Responses

Association of glycaemia with complications of type 2 diabetes: Is glycaemic treatment important?
Brian Budenholzer
bmj.com, 12 Aug 2000 [Full text]
Methodological problems
Adrian Bagust
bmj.com, 12 Oct 2000 [Full text]
Removing the influence of LADA patients will add more value to UKPDS35 findings on Type 2 diabetes related complications.
Arya K Kumarasena
bmj.com, 15 Dec 2007 [Full text]
Access jobs at BMJ Careers
Whats new online at Student BMJ