Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations.

AIMS/HYPOTHESIS: Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan. METHODS: Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur. RESULTS: SNPs in or near PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2, SLC30A8, KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 displayed significant (p < 0.05) associations with type 2 diabetes, with similar effect sizes to those seen in European populations. A constructed genetic risk score was associated with type 2 diabetes (p = 5.46 × 10(-12)), BMI (p = 2.25 × 10(-4)) and age at onset of diabetes (p = 0.002). CONCLUSIONS/INTERPRETATION: We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians. Large-scale studies and meta-analyses of South Asian populations are needed to further confirm the effect of these variants in this ethnic group.

An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference.

AIMS: A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. METHODS: We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged ≥40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. RESULTS: In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95%CI 0.24-0.67) kg/m(2) per A-allele (P=3.0 × 10(-5) ) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P=0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95%CI) 1.18 (1.07-1.30); P=0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95%CI 1.14-1.31); P=1.07 × 10(-8) ] even after adjusting for BMI [1.18 (95%CI 1.10-1.27); P=1.02 × 10(-5) ] or waist circumference [1.18 (95%CI 1.10-1.27); P=3.97 × 10(-5) ]. CONCLUSIONS: The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

Prevalence of diabetes, impaired fasting glucose and associated risk factors in a rural area of Baluchistan province according to new ADA criteria.

OBJECTIVE: To assess the prevalence of impaired fasting glucose (IFG) and diabetes in an adult rural population on the basis of fasting blood glucose (FBG) alone using American Diabetic Association (ADA) criteria and to assess the prevalence of and association between selected risk factors such as obesity, family history of diabetes and hypertension. MATERIALS AND METHODS: Sixteen randomly selected villages from the Lasbella district of Baluchistan were included in this study. One month before the survey a team visited the areas; all the households located in the selected areas were approached and the family members aged 25 or above, who were available and willing to participate in the study, were recruited. On the day of survey anthroprometric and blood pressure measurements were taken; interviews were conducted to obtain demographic information and health history and fasting blood samples were collected. The blood samples were transported to the laboratory and analysed using "GOD-PAP" Enzymatic Colorimetric test method. RESULTS: A total of 670 males and 1362 females were studied. Prevalence rate of diabetes using the ADA fasting criteria was 6.3% while the prevalence rate in males was 10.1% and in females was 4.3%. The prevalence rate of impaired fasting glucose was 4.2% in males and 2.3% in females. Overall prevalence of obesity between diabetics vs non-diabetics was 22% vs 16%, for hypertension 12.9% vs 6.5% and for positive family history of diabetes 1.6% vs 0.9% was higher among diabetics as compared to non diabetics; the difference of these parameters was statistically significant only among females (P < 0.01). CONCLUSION: The results of this study suggest the need of continual use of OGTT for screening people at high risk of developing diabetes and perhaps also for diagnosing diabetes.

Glycaemic trend during Ramadan in fasting diabetic subjects: a study from Pakistan.

The aim of this questionnaire based survey was to assess the glycaemic control care and management of our fasting diabetic subjects. This retrospective study was carried out at Baqai Institute of Diabetology and Endocrinology, its affiliated centers and Memon Diabetic Centre of Karachi. Data was collected by a questionnaire including socio-demographic data, duration of diabetes, life style, diet and treatment during and preceding Ramadan of year 2004. All Known diabetic Muslim subjects except children below 10 years were included. The subjects were asked if they had observed any of the hypoglycemic or hyperglycemic symptoms. The major severity of the symptoms was assessed depending upon the assistance needed. The plasma glucose level during these episodes was recorded where it was available. During the month of Ramadan 327 out of 453 subjects (72.5%) fasted. Mean age of subjects was 50.3 +/- 12.6 years. Average duration of diabetes was 9.3 +/- 7.3 years. Majority of the subjects (96.3%) fasted with type 2 diabetes while only 3.7% fasted with type I diabetes. Subjects fasted for an average of 25 days. Overall prevalence of hypoglycemia and hyperglycemia was 21.7 and 19.8%, respectively. Only 4.0% had major hypoglycemic episodes, while 8% had major hyperglycemic episodes. The present study suggests that all diabetic subjects who intend to fast should be counseled before Ramadan about change in medication timings and dose, dietary changes and pattern of physical activity and about role of self-monitoring of blood glucose especially during acute symptoms.