Baseline level of 30-min plasma glucose is an independent predictor of incident diabetes among Asian Indians: analysis of two diabetes prevention programmes.

BACKGROUND: The objective was to study the ability of the 30-min plasma glucose (30-min PG) during an oral glucose tolerance test to predict the future risk of type 2 diabetes among Asian Indians with impaired glucose tolerance. METHODS: For the present analyses, we utilized data from 753 participants from two diabetes primary prevention studies, having complete data at the end of the study periods, including 236 from Indian Diabetes Prevention Programme-1 and 517 from the 2013 study. Baseline 30-min PG values were divided into tertiles: T1 < 9.1 mmol/L (<163.0 mg/dL); T2 9.2-10.4 mmol/L (164.0-187.0 mg/dL) and T3 ≥ 10.4 mmol/L (≥188 mg/dL). The predictive values of tertiles of 30-min PG for incident diabetes were assessed using Cox regression analyses RESULTS: At the end of the studies, 230 (30.5%) participants developed diabetes. Participants with higher levels of 30-min PG were more likely to have increased fasting, 2-h PG and HbA1c levels, increased prevalence of impaired fasting glucose and decreased beta cell function. The progression rate of diabetes increased with increasing tertiles of 30-min PG. Cox's regression analysis showed that 30-min PG was an independent predictor of incident diabetes after adjustment for an array of covariates [Hazard Ratio (HR):1.44 (1.01-2.06)] CONCLUSIONS: This prospective analysis demonstrates, for the first time, an independent association between an elevated 30-min PG level and incident diabetes among Asian Indians with impaired glucose tolerance. Predictive utility of glycemic thresholds at various time points other than the traditional fasting and 2-h PG values should therefore merit further consideration. Copyright © 2016 John Wiley & Sons, Ltd.

Screening among male industrial workers in India shows high prevalence of impaired glucose tolerance, undetected diabetes and cardiovascular risk clustering.

OBJECTIVE: To study the magnitude of undetected diabetes, impaired glucose tolerance (IGT) and clustering of cardiometabolic risk factors among male industrial workers. METHODS: Measurements of 2h post glucose blood glucose (2h PG), blood pressure, body mass index (BMI) and waist circumference (WC) were done in 8741 non-diabetic men of 35-55 years. Presence of family history of diabetes (FH) was noted. Risk associations with diabetes and IGT were studied using multiple logistic regression analysis. Clustering of overweight/obesity, abdominal obesity, hypertension was noted. RESULTS: Prevalence of undetected diabetes (14.9%) and IGT (31.4%) were high. FH, age, hypertension and BMI showed strong associations with diabetes and IGT. More than 40% had clustering of risk factors. CONCLUSION: High prevalence of undetected diabetes, IGT and clustering of cardiometabolic risk factors among young industrial workers mandates that regular screening for metabolic disorders should be undertaken to prevent development of severe morbidity in the productive years of life.

Liraglutide-induced acute pancreatitis.

An obese lady of 51 year with Type 2 Diabetes Mellitus for 13 years was prescribed Liraglutide, a glucagon like peptide (GLP-1) analogue (Victoza) for glycaemic control and reduction of weight. She was on gliclazide and Insulin prior to initiation of Liraglutide. Eight weeks after initiation of GLP -1 analogue, she developed severe abdominal pain, nausea and vomiting. She was admitted to a private hospital and evaluated. Biochemical tests and CT scan revealed presence of pancreatitis and she was treated for acute pancreatitis. Liraglutide was withdrawn and symptoms subsided. Subsequent follow-up showed that pancreatic enzyme levels were normal.

Combining Fasting Plasma Glucose with Gamma-glutamyl Transferase Improves the Sensitivity to Predict Incident Diabetes in Asian Indian Men with Impaired Glucose Tolerance.

OBJECTIVE: To study the associations of baseline gamma-glutamyltransferase (GGT) and alanine transaminase (ALT) with incident diabetes among Asian Indian men with impaired glucose tolerance (IGT). METHODS: In a 2 year prospective, randomised, controlled primary prevention study of diabetes, among 537 IGT men aged 35-55 years, 123 incident diabetes (DM) cases occurred. Anthropometric {body mass index (BMI), waist circumference (WC)}, and laboratory measurements (fasting, 30 min and 2 hr plasma glucose (2 hr PG), HbA1c and plasma insulin, lipid profile, ALT, GGT) were estimated at baseline (Clinical Trial Identification No: NCT00819455). Predictive associations of baseline GGT and ALT values during the study were assessed using appropriate statistical methods. RESULTS: Baseline GGT but not ALT was significantly higher in incident diabetes cases. Mean (95% CI) GGT decreased in subjects who reverted to normal glucose tolerance (NGT), whereas it increased in subjects who deteriorated to diabetes (NGT:-3.5 (-6.4 to -0.6); IGT:0.3 (-3.0 to 2.4); DM:8.3 (3.6 to 13.0) UL(-1); P < 0.0001). The risk of DM significantly increased with increasing baseline GGT after adjusting for confounders such as BMI, alcohol drinking, 2 hr PG and insulin resistance (2.02[1.35-3.02]; P = 0.001). Receiver operating characteristic curve showed that the model comprising of baseline fasting plasma glucose (FPG) and GGT (area-under-curve(AUC)[95% CI]: 0.668 [0.613-0.722]; P < 0.0001) was equally sensitive in identifying subjects with risk of diabetes as compared to 2 hr PG (AUC [95% CI]: 0.670 [0.614-0.725]; P < 0.0001) and HbA1c (AUC [95% CI]: 0.677 [0.619-0.734]; P < 0.0001) alone. CONCLUSIONS: GGT was an independent predictor of incident diabetes. Combination of GGT and FPG offers a simple and sensitive tool to identify subjects at high risk of developing diabetes.

Treatment with DPP-4 inhibitors does not increase the chance of pancreatitis in patients with type 2 diabetes.

OBJECTIVES: This retrospective analysis was done in type 2 diabetes patients to study whether treatment with either sitagliptin or other Dipeptidyl peptidase-4 (DPP-4) inhibitors increased the risk of pancreatitis. Comparison with patients treated with other Oral Antidiabetic Drugs (OADs) was done. METHODS: Asian Indian type 2 diabetic subjects (duration > or = 5 years) treated with sitagliptin or other DPP-4 inhibitors (n = 957) were selected from the clinic records. Control group included patients treated with other hypoglycaemic agents and had serum lipase and/or amylase estimated (n = 718). HbA1c and serum levels of lipase and/or amylase were measured. For lipase, values > or = 90 IU/l and for amylase, values > or = 150 IU/l were considered abnormal. RESULTS: Percentages with elevated lipase values were similar among patients on sitagliptin or other gliptins and control subjects. Similar percentages of patients using DPP-4 inhibitors (6.9%) or other hypoglycaemic agents (8.2%) had elevated levels of lipase. Abnormal amylase values were more common among the control subjects vs those using DPP-4 inhibitors. CONCLUSIONS: Present analysis suggests that use of DPP-4 inhibitors is safe in patients who do not have contraindications for its use.

Reinforcement of adherence to prescription recommendations in Asian Indian diabetes patients using short message service (SMS)--a pilot study.

OBJECTIVES: To investigate the acceptability and feasibility of using short message services (SMS) via cell phones to ensure adherence to management prescriptions by diabetic patients. METHODS: Type 2 diabetic patients with 5 or more years of diabetes and having HbA1c between 7.0% to 10% were randomized to the control arm (n = 105) to receive standard care and to the intervention arm (SMS, n = 110). Messages in English on principles of diabetes management were sent once in 3 days, the contents and frequencies varied as per the patients' preferences. The study duration was 1 year. All participants were advised to report for quarterly clinic visits. A comparative assessment of the clinical, biochemical and anthropometric outcomes was made among the groups at the annual visit. RESULTS: Annual review was possible in 71% of intervention group and 63% of control group. SMS was acceptable to the patients and the median number requested was 2 per week. HbA1c and plasma lipids improved significantly in the SMS group. CONCLUSIONS: The pilot study showed that frequent communication via SMS was acceptable to diabetic patients and it helped to improve the health outcomes.

A pragmatic and scalable strategy using mobile technology to promote sustained lifestyle changes to prevent type 2 diabetes in India-Outcome of screening.

AIMS: We describe a two-step screening approach using non-invasive risk assessment and glycated hemoglobin (HbA1c) to identify participants for a diabetes prevention trial. METHODS: A total of 6030 non-diabetic persons of 35-55 years were screened using risk assessment for diabetes. Those with three or more risk factors were screened using point of care HbA1c test. For this study, participants in HbA1c categories of 6.0% (42.1 mmol/mol)-6.4% (46.4 mmol/mol) were selected and their characteristics were analyzed. RESULTS: Among 6030 persons, 2835 (47%) had three or more risk factors for diabetes. Among those screened with HbA1c, 43.2% (1225) had HbA1c values of <6.0% (42.1 mmol/mol), 46.8% (1327) had HbA1c values between 6.0% (42.1 mmol/mol) and ≤ 6.4% (46.4 mmol/mol) and 10% (283) had undiagnosed diabetes with ≥6.5% (47.5 mmol/mol). Positive family history was present in 53.2%, 81.7% were obese and 14.8% were overweight. CONCLUSIONS: Opportunistic screening using a two-step approach: diabetes risk profile and HbA1c measurement detected a large percentage of individuals with prediabetes. Prediabetic persons recruited to the trial had higher percentage of obesity and presence of positive family history than those who had lower HbA1c values. Outcomes from this trial will enable comparisons with the previous prevention studies that used blood glucose levels as the screening criteria.

Retinol binding protein-4 predicts incident diabetes in Asian Indian men with prediabetes.

The association of retinol binding protein-4 (RBP4) with incident type 2 diabetes (T2DM) in Asian Indian middle-aged men with impaired glucose tolerance (IGT) was studied. This was an ancillary analysis of a subsample from a cohort of participants with IGT in a 2 year prospective diabetes prevention program in India. For this analysis, 71 incident T2DM and 76 non-diabetic cases (non-progressors) based on the final glycemic outcome were selected. Baseline serum RBP4 was measured using competitive enzyme immunoassay. Correlations of RBP4 with relevant anthropometric and biochemical variables and also its association with diabetes were assessed using appropriate statistical analyses. Participants who developed T2DM had higher levels of serum RBP4 (21.3 [IQR: 17.7-24.9] µg/mL) compared with non-progressors (17.3 [IQR: 13.1-21.0] µg/mL; P = 0.001). Levels of RBP4 were lower than in Caucasians. Stepwise linear regression analysis showed that body mass index (BMI), systolic blood pressure, triglycerides, and HbA1c had independent associations with RBP4 levels. Multiple logistic regression analyses showed that RBP4 was independently associated with incident diabetes (odds ratio [OR] [95%confidence interval (CI)]: 1.69 [1.18-2.41]; P = 0.004). Adjustment for study group, age, BMI, waist circumference, 2 H plasma glucose, triglycerides, gamma glutamyl transferase, and insulin resistance weakened the significance of its association (OR [95%CI]: 1.65 [1.03-2.66]; P = 0.038).The results of this preliminary analyses showed that baseline serum RBP4 levels were independently associated with incident diabetes in Asian Indian men with IGT. It may be used as an additional predictor of future diabetes.

Adiponectin, leptin, interleukin-6 and HbA1c in the prediction of incident type 2 diabetes: A nested case-control study in Asian Indian men with impaired glucose tolerance.

AIMS: The aims of this study were: (1) to assess the association of adiponectin, leptin and interleukin-6 (IL-6) with incidence of type 2 diabetes (T2DM) in Asian Indian men with impaired glucose tolerance (IGT) and (2) to evaluate the additional contribution of these with the well-established glycaemic marker HbA1c. METHODS: This is an ancillary analyses of a nested case-control study derived from a prospective, prevention trial in India. All the participants had IGT at baseline. For this subanalysis a total of 147 (T2DM: 71; nondiabetic: 76) participants were selected based on the final glycemic outcomes. Association of these selected adipokines with T2DM were assessed using logistic regression analyses. Clinical usefulness of adding adipokine markers with HbA1c on prediction of T2DM was assessed using the area under the curve (AUC) of the receiver operating characteristics. RESULTS: Baseline levels of adiponectin were lower and the levels of IL-6 were higher in T2DM cases when compared with non-diabetic cases (P<0.05). Levels of leptin were similar in both groups. In fully adjusted models, adiponectin (odds ratio (OR): 0.55 [95%CI: 0.33-0.91]; P=0.019) and IL-6 (OR: 2.27 [95%CI: 1.40-3.691]; P=0.001) were associated with diabetes. Addition of adiponectin to HbA1c improved the AUC (ΔAUC: 0.0619; P=0.0251), whereas addition of IL-6 did not improve the predictive power of HbA1c alone. CONCLUSIONS: Adiponectin and IL-6 are independently associated with incident diabetes. However, they are unlikely to serve as simple tools to predict future risk of diabetes but may have a role in understanding the pathogenesis.

The oral disposition index is a strong predictor of incident diabetes in Asian Indian prediabetic men.

AIMS: In this analysis, we sought to examine the prospective association of the disposition index (DIo) derived from oral glucose tolerance test with incident diabetes in Asian Indian men with impaired glucose tolerance (IGT). METHODS: These post hoc analyses used data from a 2-year prospective study in primary prevention of diabetes using lifestyle intervention among 517 men with IGT. All the participants received standard lifestyle advice at baseline. The surrogate insulin sensitivity and insulin secretion measures were tested for their hyperbolic relationship. Predictive associations of various surrogate measures with incident diabetes were determined using receiver operating characteristic curves. RESULTS: The combination of total area under the curve of insulin-to-glucose ratio (AUCinsulin/glucose) and Matsuda's insulin sensitivity index was the best equation to depict DIo [ß: -0.954 (95 % CI -1.015 to -0.893)] compared to other measures tested in this cohort. There was an inverse association between change in DIo at the final follow-up and development of incident diabetes. Among the surrogate insulin measures studied, DIo [AUC (0.717 (95 % CI 0.675-0.756))] as a composite measure was superior than other surrogate indices. CONCLUSIONS: Among the surrogate indices studied, DIo was the best measure associated with incident diabetes.

Early improvement predicts reduced risk of incident diabetes and improved cardiovascular risk in prediabetic Asian Indian men participating in a 2-year lifestyle intervention program.

OBJECTIVE: Objectives of this ancillary analysis of a prospective, prevention study among Asian Indians with impaired glucose tolerance (IGT) were a) to quantify the reduction in incident diabetes at 24 months in participants who achieved normal glucose tolerance (NGT) at 6 months (NGT-6 m) compared with the other participants, b) the factors influencing the reversal to NGT at the end of the study at 24 months (NGT-24 m), and c) to assess changes in cardiometabolic risk factors in different categories of dysglycemia at 24 months. RESEARCH DESIGN AND METHODS: Data from a 2-year primary prevention trial were used. Effect of reversion to NGT-6 m on incidence of type 2 diabetes mellitus (T2DM) was analyzed using the Cox proportional hazards model. Predictive variables for reversal to NGT were identified using multiple logistic regression analysis. Changes in cardiometabolic risk factors were estimated according to the final glycemic status using fixed-effect, mixed-linear regression modeling. RESULTS: The risk of T2DM in 2 years was lower by 75% in NGT-6 m group (hazard ratio 0.25 [95% CI 0.12-0.52]). Predictive variables for reversal to NGT-24 m were good baseline ß-cell function (odds ratio [OR] 2.79 [95% CI 2.30-3.40]) and its further improvement (OR 5.70 [95% CI 4.58-7.08]), and NGT-6 m (OR 2.10 [95% CI 1.14-3.83]). BMI decreased in those who reverted to NGT. Deterioration to T2DM was associated with an increase in the levels of cardiometabolic risk factors. CONCLUSIONS: Early reversion to NGT by lifestyle intervention in prediabetic men was associated with a significant reduction in subsequent incidence of diabetes. Good baseline ß-cell function and its further improvement and NGT-6 m were associated with reversion to NGT-24 months. Reversion to NGT was associated with modest improvements, whereas conversion to T2DM was associated with significant worsening of the cardiometabolic risk profile.

Improvement in diet habits, independent of physical activity helps to reduce incident diabetes among prediabetic Asian Indian men.

AIMS: To assess the beneficial effects of the components of lifestyle intervention in reducing incidence of diabetes in Asian Indian men with impaired glucose tolerance (IGT) in India. METHODS: This analysis was based on a 2 year prospective, randomized controlled primary prevention trial in a cohort of Asian Indian men with IGT (n=537) (Clinical Trial No: NCT00819455). Intervention and control groups were given standard care advice at baseline. Additionally, the intervention group received frequent, mobile phone based text message reminders on healthy lifestyle principles. Dietary intake and physical activity habits were recorded by validated questionnaires. The lifestyle goals were: reductions in consumption of carbohydrates, oil, portion size and body mass index of at least 1 unit (1 kg/m(2)) from baseline and maintenance of good physical activity. The association between diabetes and lifestyle goals achieved was assessed using multiple logistic regression analyses. Changes in insulin sensitivity (Matsuda's insulin sensitivity index) and oral disposition index during the follow-up were assessed. RESULTS: At the end of the study, 123 (23.8%) participants developed diabetes. The mean lifestyle score was higher in the intervention group compared with control (2.59 ± 1.13 vs. 2.28 ± 1.17; P=0.002). Among the 5 lifestyle variables, significant improvements in the 3 dietary goal were seen with intervention. Concomitant improvement in insulin sensitivity and oral disposition index was noted. Higher lifestyle score was associated with lower risk of developing diabetes (odds ratio: 0.54 [95% CI: 0.44-0.70]; P<0.0001). CONCLUSIONS: Beneficial effects of intervention were associated with increased compliance to lifestyle goals. The plausible mechanism is through improvement in insulin sensitivity and beta cell preservation.

Effectiveness of mobile phone messaging in prevention of type 2 diabetes by lifestyle modification in men in India: a prospective, parallel-group, randomised controlled trial.

BACKGROUND: Type 2 diabetes can often be prevented by lifestyle modification; however, successful lifestyle intervention programmes are labour intensive. Mobile phone messaging is an inexpensive alternative way to deliver educational and motivational advice about lifestyle modification. We aimed to assess whether mobile phone messaging that encouraged lifestyle change could reduce incident type 2 diabetes in Indian Asian men with impaired glucose tolerance. METHODS: We did a prospective, parallel-group, randomised controlled trial between Aug 10, 2009, and Nov 30, 2012, at ten sites in southeast India. Working Indian men (aged 35-55 years) with impaired glucose tolerance were randomly assigned (1:1) with a computer-generated randomisation sequence to a mobile phone messaging intervention or standard care (control group). Participants in the intervention group received frequent mobile phone messages compared with controls who received standard lifestyle modification advice at baseline only. Field staff and participants were, by necessity, not masked to study group assignment, but allocation was concealed from laboratory personnel as well as principal and co-investigators. The primary outcome was incidence of type 2 diabetes, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00819455. RESULTS: We assessed 8741 participants for eligibility. 537 patients were randomly assigned to either the mobile phone messaging intervention (n=271) or standard care (n=266). The cumulative incidence of type 2 diabetes was lower in those who received mobile phone messages than in controls: 50 (18%) participants in the intervention group developed type 2 diabetes compared with 73 (27%) in the control group (hazard ratio 0·64, 95% CI 0·45-0·92; p=0·015). The number needed to treat to prevent one case of type 2 diabetes was 11 (95% CI 6-55). One patient in the control group died suddenly at the end of the first year. We recorded no other serious adverse events. INTERPRETATION: Mobile phone messaging is an effective and acceptable method to deliver advice and support towards lifestyle modification to prevent type 2 diabetes in men at high risk. FUNDING: The UK India Education and Research Initiative, the World Diabetes Foundation.

Trends in prevalence of diabetes in Asian countries.

Diabetes is a major lifestyle disorder, the prevalence of which is increasing globally. Asian countries contribute to more than 60% of the world's diabetic population as the prevalence of diabetes is increasing in these countries. Socio-economic growth and industrialization are rapidly occurring in many of these countries. The urban-rural divide in prevalence is narrowing as urbanization is spreading widely, adversely affecting the lifestyle of populations. Asians have a strong ethnic and genetic predisposition for diabetes and have lower thresholds for the environmental risk factors. As a result, they develop diabetes at a younger age and at a lower body mass index and waist circumference when compared with the Western population. The adverse effect of physical inactivity and fatty food are manifested as the increasing rate of overweightness and obesity, even among children. The health care budgets for the disease management are meager and the health care outcome is far from the optimum. As a result, complications of diabetes are common and the economic burden is very high, especially among the poor strata of the society. National endeavors are urgently needed for early diagnosis, effective management and for primary prevention of diabetes. This editorial aims to highlight the rising trend in prevalence of diabetes in Asia, its causative factors and the urgent need to implement national strategies for primary prevention of type 2 diabetes.

Hypertriglyceridaemia either in isolation or in combination with abdominal obesity is strongly associated with atherogenic dyslipidaemia in Asian Indians.

AIM: To assess the prevalence of isolated hypertriglyceridaemia (iHTG) and hypertriglyceridaemic waist phenotype (HTWP) in urban adult Asian Indian population and to study their associations with atherogenic dyslipidaemia. METHODS: Data of an epidemiological survey (n=2117, M:F 1007:1110) was used. Prevalences of iHTG (fasting triglycerides (TG) ≥ 1.7 mmol/l) and HTWP (waist circumference male ≥ 90 cm and female ≥ 80 cm and TG ≥ 1.7 mmol/l), were assessed. Their prevalences in relation to glucose intolerance were also studied. Associations of iHTG and HTWP with the occurrence of atherogenic dyslipidaemia indicated by elevated LDL-C/HDL-C ratio of ≥2.5 were assessed using multiple logistic regression analyses. RESULTS: iHTG, and HTWP were present in 13.4% and 17.8% respectively. Prevalence of HTWP was significantly higher among women. Prevalence of HTWP progressively increased with glucose intolerance. Nearly 60% of the subjects with iHTG or HTWP had atherogenic dyslipidaemia and prevalence was similar in both groups. CONCLUSIONS: Hypertriglyceridaemia, present either as iHTG or HTWP was strongly associated with atherogenic dyslipidaemia. Dyslipidaemia occurred more frequently in glucose intolerance since the prevalence of both forms of hypertriglyceridaemia increased with glucose intolerance.

Efficacy of primary prevention interventions when fasting and postglucose dysglycemia coexist: analysis of the Indian Diabetes Prevention Programmes (IDPP-1 and IDPP-2).

OBJECTIVE: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have different pathophysiological abnormalities, and their combination may influence the effectiveness of the primary prevention tools. The hypothesis was tested in this analysis, which was done in a pooled sample of two Indian Diabetes Prevention Programmes (IDPP-1 and IDPP-2). RESEARCH DESIGN AND METHODS: Researchers analyzed and followed up on the details of 845 of the 869 IGT subjects in the two studies for 3 years. Incidence of diabetes and reversal to normoglycemia (normal glucose tolerance [NGT]) were assessed in group 1 with baseline isolated IGT (iIGT) (n = 667) and in group 2 with IGT + IFG (n = 178). The proportion developing diabetes in the groups were analyzed in the control arm with standard advice (IDPP-1) (n = 125), lifestyle modification (LSM) (297 from both), metformin (n = 125, IDPP-1), and LSM + metformin (n = 121, IDPP-1) and LSM + pioglitazone (n = 298, IDPP-2). Cox regression analysis was used to assess the influence of IGT + IFG versus iIGT on the effectiveness of the interventions. RESULTS: Group 2 had a higher proportion developing diabetes in 3 years (56.2 vs. 33.6% in group 1, P = 0.000) and a lower rate of reversal to NGT (18 vs. 32.1%, P = 0.000). Cox regression analysis showed that effectiveness of intervention was not different in the presence of fasting and postglucose glycemia after adjusting for confounding variables. CONCLUSIONS: The effectiveness of primary prevention strategies appears to be similar in subjects with iIGT or with combined IGT + IFG. However, the possibility remains that a larger study might show that the effectiveness is lower in those with the combined abnormality.