Gamma-glutamyltransferase and diabetes—a 4 year follow-up study

AIMS/HYPOTHESIS: Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. However, more subtle gradations in GGT could be informative because its expression is enhanced by oxidative stress and it could be released by several conditions inducing cellular stress. Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes. METHODS: A total of 4,088 healthy men working in a steel manufacturing company were examined in 1994 and 1998. Diabetes was defined as a serum fasting glucose concentration of more than 126 mg/dl or the use of diabetes medication. RESULTS: There was a strong dose-response relation between serum GGT concentrations at baseline and the incidence of diabetes. In contrast to the 31% of men with GGT concentrations under 9 U/l, adjusted relative risks for incidence of diabetes for GGT concentrations 10-19, 20-29, 30-39, 40-49, and over 50 U/l were 8.0, 13.3, 12.6, 19.6 and 25.8, respectively. The associations of age and BMI with incident diabetes became stronger the higher the value of baseline serum GGT concentration. CONCLUSION/INTERPRETATION: This study suggests that an increase in GGT concentration within its physiological range is a sensitive and early biomarker for the development of diabetes.     

Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?

Prior to the development of type 2 diabetes, glucose levels increase into the prediabetic states of isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), or combined IFG/IGT. A better understanding of the aetiology and pathophysiology of the prediabetic states might give a basis for the development of individualised prevention and treatment strategies for type 2 diabetes. Several studies have examined mechanisms and potential aetiological factors leading to the development of the different prediabetic states. The pathophysiology of i-IFG seems to include the following key defects: reduced hepatic insulin sensitivity, stationary beta cell dysfunction and/or chronic low beta cell mass, altered glucagon-like peptide-1 secretion and inappropriately elevated glucagon secretion. Conversely, the prediabetic state i-IGT is characterised by reduced peripheral insulin sensitivity, near-normal hepatic insulin sensitivity, progressive loss of beta cell function, reduced secretion of glucose-dependent insulinotropic polypeptide and inappropriately elevated glucagon secretion. Individuals developing combined IFG/IGT exhibit severe defects in both peripheral and hepatic insulin sensitivity as well as a progressive loss of beta cell function. The aetiologies of i-IFG and i-IGT also seem to differ, with i-IFG being predominantly related to genetic factors, smoking and male sex, while i-IGT is predominantly related to physical inactivity, unhealthy diet and short stature. Since the transition from the prediabetic states to overt type 2 diabetes is characterised by a non-reversible vicious cycle that includes severe deleterious effects on glucose metabolism, there are good reasons to use the well-established aetiological and pathophysiological differences in i-IFG, i-IGT and IFG/IGT to design individualised preventive strategies.     

Trends in the prevalence of diabetes and impaired fasting glucose in association with obesity in Iran: 2005–2011

Aims

To estimate the prevalence and trends of diabetes mellitus (DM) and impaired fasting glucose (IFG), 2005–2011, and to determine the contribution of obesity to DM prevalence.

Patients and methods

Data from Surveillance of Risk Factors of Non-communicable Diseases (SuRFNCD) conducted in 2005, 2007, and 2011 were gathered. DM was defined as presence of self-reported previous diagnosis or a fasting plasma glucose (FPG) ≥ 7 mmol/L. IFG was diagnosed with FPG levels between 5.6 and 6.9 mmol/L. Prevalence rates for 2011 and trends for 2005–2011 were determined by extrapolating survey results to Iran's adult population. Population attributable fraction (PAF) of obesity was also calculated.

Results

In 2011, IFG and total DM prevalence rates were 14.60% (95%CI: 12.41–16.78) and 11.37% (95%CI: 9.86–12.89) among 25–70 years, respectively. DM was more common in older age (p < 0.0001), in women (p = 0.0216), and in urban-dwellers (p = 0.0001).In 2005–2011, trend analysis revealed a 35.1% increase in DM prevalence (OR: 1.04, 95%CI: 1.01–1.07, p = 0.011); albeit, IFG prevalence remained relatively unchanged (OR: 0.98, 95%CI: 0.95–1.00, p = 0.167). In this period, DM awareness improved; undiagnosed DM prevalence decreased from 45.7% to 24.7% (p < 0.001). PAF analysis demonstrated that 33.78%, 10.25%, and 30.56% of the prevalent DM can be attributed to overweight (BMI ≥ 25 kg/m²), general obesity (BMI ≥ 30 kg/m²), and central obesity (waist circumference ≥ 90 cm), respectively. Additionally, the DM increase rate in 2005–2011, was 20 times higher in morbidly obese compared with lean individuals.

Conclusion

More than four million Iranian adults have DM which has increased by 35% over the past seven years, owing in large part, to expanding obesity epidemic.     

Prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in urban and rural India: Phase I results of the Indian Council of Medical Research�CINdia DIABetes (ICMR�CINDIAB) study

Aims/hypothesis

This study reports the results of the first phase of a national study to determine the prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in India.

Methods

A total of 363 primary sampling units (188 urban, 175 rural), in three states (Tamilnadu, Maharashtra and Jharkhand) and one union territory (Chandigarh) of India were sampled using a stratified multistage sampling design to survey individuals aged ??20?years. The prevalence rates of diabetes and prediabetes were assessed by measurement of fasting and 2?h post glucose load capillary blood glucose.

Results

Of the 16,607 individuals selected for the study, 14,277 (86%) participated, of whom 13,055 gave blood samples. The weighted prevalence of diabetes (both known and newly diagnosed) was 10.4% in Tamilnadu, 8.4% in Maharashtra, 5.3% in Jharkhand, and 13.6% in Chandigarh. The prevalences of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were 8.3%, 12.8%, 8.1% and 14.6% respectively. Multiple logistic regression analysis showed that age, male sex, family history of diabetes, urban residence, abdominal obesity, generalised obesity, hypertension and income status were significantly associated with diabetes. Significant risk factors for prediabetes were age, family history of diabetes, abdominal obesity, hypertension and income status.

Conclusions/interpretations

We estimate that, in 2011, Maharashtra will have 6 million individuals with diabetes and 9.2 million with prediabetes, Tamilnadu will have 4.8 million with diabetes and 3.9 million with prediabetes, Jharkhand will have 0.96 million with diabetes and 1.5 million with prediabetes, and Chandigarh will have 0.12 million with diabetes and 0.13 million with prediabetes. Projections for the whole of India would be 62.4 million people with diabetes and 77.2 million people with prediabetes.     

HbA<Subscript>1c</Subscript> and cardiovascular risk score identify people who may benefit from preventive interventions: a 7 year follow-up of a high-risk screening programme for diabetes in primary care (ADDITION), Denmark

Aims/hypothesis  

The measurement of HbA_1c is suggested as a diagnostic test for diabetes. Screening for diabetes also identifies individuals with elevated cardiovascular risk but who are free of diabetes. This study aims to assess whether screening by HbA_1c or glucose measures alone, or in combination with a cardiovascular risk assessment, identifies people who may benefit from preventive interventions, i.e. people with screen detected diabetes and people belonging to groups with excess mortality, during a median follow-up of 7 years.     

Determinants of the progression to type 2 diabetes and regression to normoglycemia in people with pre-diabetes: A population‐based cohort study over ten years

AimsTo determine the rates and predictors of the regression to normoglycemia and progression to diabetes among subjects with pre-diabetes.MethodsA 10-year longitudinal population-based study was conducted among 1329 participants with pre-diabetes in the Tehran Lipid and Glucose Study. Pre-diabetes was divided into isolated IFG (iIFG), isolated IGT (iIGT), and combined IFG/IGT. Univariate and stepwise multivariable Cox regression was used to evaluate predictors of glycemic conversions.ResultsThe cumulative incidences of normoglycemia and diabetes were 43.7% (95%CI 40.9–46.4) and 40.1% (37.3–42.7), respectively. Isolated IGT returned to normoglycemia more than iIFG (HR:1.26, 1.05–1.51), but there was no difference in how quickly they progressed to diabetes. Regression to normoglycemia was associated with younger age, female sex, lower BMI, no familial history of diabetes, higher HDL-C, and ex-smoking. Older age, higher BMI, diastolic blood pressure, total cholesterol, lower HDL-C, and familial history for diabetes were associated with progression to diabetes. The influence of BMI on glycemic status conversions diminished with age. At approximately above 60 years old, the hazards of BMI for any conversions faded out.ConclusionsThe modifiable predictors of regression to normoglycemia and progression to diabetes are roughly the same. The importance of BMI attenuates in elderly subjects.     

Is fasting glucose level during oral glucose tolerance test an indicator of the insulin need in gestational diabetes?

Maintenance of a good metabolic control improves foetal and maternal outcomes in gestational diabetes mellitus (GDM). The aim of this study is to investigate the utility of diagnostic oral glucose tolerance test (OGTT) in prediction of the need of insulin in patients with GDM. One hundred and fifty five consecutive patients with GDM were included in the study. Patients were ordered MNT first. Those who failed to maintain glycemic targets were treated with insulin. Glucose levels obtained from the diagnostic OGTT were evaluated regarding the need of insulin during the rest of pregnancy. Fasting, 1h and 3h post-load glucose levels were significantly elevated in patients who required insulin. Multivariate analysis showed that fasting glucose level on OGTT was an independent predictor for the insulin need. A cut-off value of 105mg/dl had a fair specificity (91.89%) and positive predictive value (80.64%) for the prediction of patients who required insulin during the rest of their pregnancy. Our results suggest that fasting glucose level on OGTT is a predictor of the need for insulin treatment in GDM. A cut-off level of 105mg/dl seems to effectively determine high-risk patients for additional treatment other than MNT in GDM.     

Incidence and progression of diabetic retinopathy in Japanese adults with type 2 diabetes: 8 year follow-up study of the Japan Diabetes Complications Study (JDCS)

Aims/hypothesis  

The aim of this study was to determine the incidence and progression rates of diabetic retinopathy and their associations in Japanese individuals with type 2 diabetes.     

High prevalence of impaired fasting glucose and type 2 diabetes mellitus in Penghu Islets, Taiwan: evidence of a rapidly emerging epidemic?

The purpose of this study was to estimate the prevalence of type 2 diabetes and impaired fasting glucose (IFG) in Penghu, Taiwan and compare these estimates with those of the US (NHANES III). Diabetes and IFG (American Diabetes Association criteria, 1997) were assessed among a stratified random sample of 2500 residents of Penghu Islands, Taiwan. The prevalence (age-adjusted to world adult population) of diabetes and IFG were 16.8% (95% CI 15.0-18.6) and 21.0% (95% CI 19.0-23.0), respectively, among Penghu Islanders in Taiwan. Age sex-specific diabetes prevalence ranged from 10.0% in men aged 40-49 years to 29.4% in women aged 60-69 years. Prevalence of IFG ranged from 14.7% in women aged 40-49 years to 30.7% in men aged 50-59 years. Age, body mass index (BMI), and family history of diabetes were each independently associated with both diabetes and IFG. In addition, female gender, apolipoprotein B and triglyceride concentrations were associated with diabetes, and hypertension and apolipoprotein B concentration with IFG. Among persons > or = 40 years in Penghu, Taiwan, the prevalence of diabetes is up to a third higher and the prevalence of IFG is up to three times higher than comparably aged Americans, despite their having a mean BMI 2.2-3.2 kg/m2 lower than Americans. The alarmingly high prevalence of IFG in Taiwan may indicate an emerging diabetes epidemic.     

Leisure-time physical activity and type 2 diabetes during a 28 year follow-up in twins

Aims/hypothesis  

The study aimed to investigate whether baseline physical activity protects against the occurrence of type 2 diabetes during a 28 year follow-up, after controlling for childhood environment and genetic predisposition.     

Structured personal care of type 2 diabetes: a 19 year follow-up of the study Diabetes Care in General Practice (DCGP)

Aims/hypothesis

This study is a 19 year observational follow-up of a pragmatic open multicentre cluster-randomised controlled trial of 6 years of structured personal diabetes care starting from diagnosis.

Methods

A total of 1,381 patients aged ≥40 years and newly diagnosed with type 2 diabetes were followed up in national registries for 19 years. Clinical follow-up was at 6 and 14 years after diabetes diagnosis. The original 6 year intervention included regular follow-up and individualised goal setting, supported by prompting of doctors, clinical guidelines, feedback and continuing medical education (ClinicalTrials.gov NCT01074762). The registry-based endpoints were: incidence of any diabetes-related endpoint; diabetes-related death; all-cause mortality; myocardial infarction (MI); stroke; peripheral vascular disease; and microvascular disease.

Results

At 14 year clinical follow-up, group differences in risk factors from the 6 year follow-up had levelled out, although the prevalence of (micro)albuminuria and level of triacylglycerols were lower in the intervention group. During 19 years of registry-based monitoring, all-cause mortality was not different between the intervention and comparison groups (58.9 vs 62.3 events per 1,000 patient-years, respectively; for structured personal care, HR 0.94, 95% CI 0.83, 1.08, p?=?0.40), but a lower risk emerged for fatal and non-fatal MI (27.3 vs 33.5, HR 0.81, 95% CI 0.68, 0.98, p?=?0.030) and any diabetes-related endpoint (69.5 vs 82.1, HR 0.83, 95% CI 0.72, 0.97, p?=?0.016). These differences persisted after extensive multivariable adjustment.

Conclusions/interpretation

In concert with features such as prompting, feedback, clinical guidelines and continuing medical education, individualisation of goal setting and drug treatment may safely be applied to treat patients newly diagnosed with type 2 diabetes to lower the risk of diabetes complications.     

Impact of changes in metabolic control on progression to photocoagulation for clinically significant macular oedema: a 20 year study of type 1 diabetes

Aims/hypothesis

Although increasing hyperglycaemia, arterial hypertension and longer duration of diabetes raise the risk of progression of diabetic retinopathy, short-term benefits in terms of improved metabolic control and lowered blood pressure have not been demonstrated. We therefore examined the effect of changes in glycaemia and arterial blood pressure on the incidence of clinically significant macular oedema in a population of diabetic patients.

Methods

We performed a retrospective review of all patients with type 1 diabetes who attended the retinopathy screening clinic at the Steno Diabetes Center from 1988 to 2008, using the endpoint referral to first photocoagulation treatment for clinically significant diabetic macular oedema. The analysis included 1,878 patients (median observation, 8 years). Changes were defined as the inter-visit change; in the case of an event the last event-free interval before referral, where the median screening interval was 6 months.

Results

Risk of progression to photocoagulation for macular oedema increased with duration of diabetes (p?<?0.001), current HbA_1c (p?<?0.0001) and with the magnitude of changes in HbA_1c (p?=?0.0002) and systolic blood pressure (p?<?0.0001) in a multiple regression model. A recent decrease of ≥0.5 percentage points or an increase in HbA_1c of >0.5 percentage points per 6 months was associated with HRs of 3.04 and 1.28, respectively, compared with lesser changes in HbA_1c.

Conclusions/interpretation

In this study, large recent changes in metabolic control and systolic blood pressure, irrespective of direction, were independent risk factors for progression to photocoagulation for diabetic macular oedema. The effects of metabolic and haemodynamic stability on diabetic retinopathy should be examined in prospective studies.     

HbA1c as predictor of all-cause mortality in individuals at high risk of diabetes with normal glucose tolerance, identified by screening: a follow-up study of the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION), Denmark

Aims/hypothesis  

Stepwise screening for type 2 diabetes will not only identify people with the disease or some other form of dysglycaemia (impaired fasting glucose or impaired glucose tolerance), but also many individuals who are phenotypically at high risk of developing diabetes, but currently have normal glucose tolerance (NGT). We therefore sought to assess whether HbA_1c adds prognostic information in relation to all-cause mortality in people who have NGT and a high risk of type 2 diabetes mellitus.     

Should the lower limit of impaired fasting glucose be reduced from 110 mg/dL in Korea?

The aims of this study were to determine if impaired fasting glucose should be redefined as a fasting plasma glucose (FPG) of 100 to 125 mg/dL (5.6-6.9 mmol/L) in Korea. A prospective cohort study was undertaken involving 13189 male workers aged 30 to 59 years who did not have medication for diabetes, a history of any cancer, or a fasting glucose level of 126 mg/dL or higher at the initial examination between January 1999 to December 2000. Subjects were reexamined at periodic annual health examination over a 5-year period. The receiver operating characteristic curve for predicting the future onset of diabetes was derived by plotting the sensitivity against 1 - specificity for a baseline FPG of less than 126 mg/dL. The age- and body mass index-adjusted incidence density of type 2 diabetes mellitus was examined according to the percentile of the distribution for the baseline FPG. The baseline FPG for predicting the future onset of diabetes at a point on the receiver operating characteristic curve that was closest to the ideal 100% sensitivity and 100% specificity was 92 mg/dL. There was a threshold for the age- and body mass index-adjusted incidence density of diabetes in the group with FPG of 93 to 95 mg/dL, at a mean of 93.9 mg/dL. Lowering the lower limit of impaired fasting glucose to 100 mg/dL (5.6 mmol/L) would optimize its sensitivity and specificity for predicting the future onset of diabetes in Korea.     

Association of fasting serum insulin and cancer mortality in a healthy population – 28-year follow-up of the French TELECOM Study

Aims

Epidemiologic, pharmacoepidemiologic and pathophysiologic evidence points consistently to an association between type 2 diabetes and cancer. This association could be explained by hyperinsulinemia induced by insulin resistance. We studied the association between fasting serum insulin (FSI) and cancer mortality in a population of non-diabetic individuals.

Correlations between A1c,fasting glucose, 2h postload glucose,and β-cell function in the Chinese population

This study was aimed to assess the associations of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and 2h postload plasma glucose (2hPG) with β-cell function in the Chinese population. A total of 913 subjects underwent 75-g oral glucose tolerance test (OGTT) and HbA1c testing. According to OGTT, isolated impaired fasting glucose (i-IFG) was defined as 5.6 mmol/l ≤ FPG < 7.0 mmol/l and 2hPG < 7.8 mmol/l; isolated impaired glucose tolerance (i-IGT) was defined as FPG < 5.6 mmol/l and 7.8 mmol/l ≤ 2hPG < 11.1 mmol/l. HbA1c 5.7–6.4 % was used to identify subjects with prediabetes. Insulin release was calculated by basal homeostasis model assessment of insulin secretion (HOMA-β), early-phase InsAUC₃₀/GluAUC₃₀, and total-phase InsAUC₁₂₀/GluAUC₁₂₀. β-cell function relative to insulin sensitivity was expressed as disposition index (DI). All indices of insulin sensitivity and β-cell function gradually decreased with increasing HbA1c, FPG, and 2hPG (all p < 0.01). β-cell function decreased precipitously when HbA1c exceeded 5.5 %. Compared with HbA1c, FPG showed stronger correlations with HOMA-β, InsAUC₃₀/GluAUC₃₀, InsAUC₁₂₀/GluAUC₁₂₀, DI₃₀, and DI₁₂₀ (all p < 0.05), and 2hPG was more closely related to DI₃₀ and DI₁₂₀ (all p < 0.01). Moreover, FPG was more strongly related to HOMA-β and InsAUC₃₀/GluAUC₃₀ than 2hPG (all p < 0.05). The combination of i-IFG and HbA1c 5.7–6.4 % showed the greatest reduction in DI₃₀ and DI₁₂₀ compared with HbA1c 5.7–6.4 % alone, i-IGT, or i-IFG (p < 0.05). In conclusion, HbA1c could be used as a marker to identify subjects with impaired β-cell function, but OGTT performs better than HbA1c. The combination of HbA1c and FPG is a simple and sensitive method to evaluate β-cell function.