Diabetes in Pre-independence India: Rediscovering a Forgotten Era.

Around 300- 400 AD, ancient Indian physicians described a condition akin to diabetes mellitus which was called "Madhumeha". Sushrutha and Charaka, are also credited with describing two types of diabetes which would roughly correspond to type 1 diabetes and type 2 diabetes. However, little is known about the history of diabetes in India between the first and 19th century AD. A thorough search of literature revealed a large number of publications on diabetes from India in the 1800s and early 1900s, mostly from Calcutta and the Madras Presidency, suggesting that the prevalence of diabetes was high in these two places. Building on the observations made by a number of English physicians, Chunilal Bose in 1907 suggested the link between diabetes and lifestyle in India. Amazingly, India did not have to wait long after the discovery of insulin by Banting and Best at Toronto in 1921, to get its own supply. Around this time, Dr. J.P. Bose, eminent physician and diabetologist from Calcutta made remarkable contributions to the study of diabetes in India. He was also the first to describe the dramatic effects of insulin administration to children with type 1 diabetes in India. All these facts have remained largely forgotten which prompted the authors to delve deep into the history of diabetes in pre-independence India. This has led to the unearthing of several pearls of knowledge which are presented in this article as a fitting tribute to the 100th year of Insulin Discovery.

The -866G/A polymorphism in the promoter of the UCP2 gene is associated with risk for type 2 diabetes and with decreased insulin levels.

BACKGROUND AND AIM: Oxidative stress and impaired insulin secretion is an underlying major risk factor for the development of type 2 diabetes (T2D). Uncoupling protein-2 (UCP2) is involved in the regulation of reactive oxygen species production, insulin secretion, and lipid metabolism. Based on this we aimed to find an association of UCP2 (G-866A) polymorphism with the risk of T2D in South Indian population. METHODS: A total of 318 T2D patients and 312 controls were enrolled in this study. All the study subjects were genotyped for UCP2 (G-866A) polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Fasting blood glucose, HbA1c, serum lipid profile, systolic and diastolic blood pressure were measured by standard biochemical methods. Fasting serum insulin level was measured by ELISA. RESULTS: In UCP2 (G-866A) polymorphism, the distribution of GA (46%) and AA (14%) genotypes were significantly higher in T2D patients than the healthy controls. The frequency of GA and AA genotypes have high risk towards the development of T2D with an Odds Ratio (OR) of 1.55 (P = 0.01) and 2.04 (P = 0.01) respectively. Moreover, SNP-866 G>A allele was found to be significantly associated with T2D (OR = 1.48, P = 0.001, 95% CI = 1.16-1.88). Further, the UCP2 AA genotype showed significantly decreased level of insulin by the reduction in pancreatic ß-cell function in T2D patients. CONCLUSION: UCP2 (G-866A) polymorphism may play a crucial role in the pathogenesis of insulin secretion thus leads to the development of T2D.

Association of paraoxonase-1 gene polymorphisms with insulin resistance in South Indian population.

BACKGROUND AND AIM: Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population. METHODS: Two hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA. RESULTS: The distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P < 0.005) and 2.24 (P < 0.005) respectively. SNP 192 Q > R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients. CONCLUSION: PON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population.

Comparison of maternal and fetal outcomes among Asian Indian pregnant women with or without gestational diabetes mellitus: A situational analysis study (WINGS-3).

AIM: To compare the existing maternal and fetal outcomes in Asian Indian women with or without gestational diabetes mellitus (GDM) before the development of the Women in India with GDM Strategy (WINGS) GDM model of care (MOC). MATERIALS AND METHODS: Records of pregnant women were extracted retrospectively from three maternity centers in Chennai. GDM was diagnosed using the International Association for Pregnancy Study Groups criteria or the Carpenter and Coustan criteria. Demographic details, obstetric history, antenatal follow-up, treatment for GDM, and outcomes of delivery were collected from the electronic medical records. RESULTS: Of the 3642 records analyzed, 799 (21.9%) had GDM, of whom 456 (57.1%) were treated with insulin and medical nutrition therapy (MNT), 339 (42.4%) with MNT alone, and 4 (0.5%) with metformin. Women with GDM were older than those without (28.5 ± 4.5 vs. 27.1 ± 4.5 years; P < 0.001) and had higher mean body mass index at first booking (26.4 ± 5.2 kg/m(2) vs. 25.2 ± 5.1 kg/m(2); P < 0.001). Rates of cesarean section (26.2% vs. 18.7%; P < 0.001), preeclampsia (1.8% vs. 0.8%; P = 0.04), and macrosomia (13.9% vs. 10.8%; P = 0.02) were significantly higher among women with GDM. In women with GDM treated with insulin and MNT, emergency cesarean section (16.2% vs. 36.6%; P < 0.0001), preeclampsia (0.7% vs. 3.2%; P = 0.015), and macrosomia (9.9% vs. 18.6%; P = 0.0006) were significantly lesser compared to those treated with MNT alone. CONCLUSION: Pregnancy outcomes were in general worse in GDM women. Treatment with insulin was associated with a significantly lower risk of complications. However, in countries with limited access to insulin and other medicines may lead to poor follow-up and management of GDM. Data from this retrospective study will form the basis for the development of the WINGS GDM MOC, which will address these gaps in GDM care in low-resource settings.

Comparison of the world health organization and the International association of diabetes and pregnancy study groups criteria in diagnosing gestational diabetes mellitus in South Indians.

AIM: We aimed to compare the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and the World Health Organization (WHO) criteria to diagnose gestational diabetes mellitus (GDM) in Chennai, India. MATERIALS AND METHODS: We reviewed the retrospective data of 1351 pregnant women who underwent screening for GDM at four selected diabetes centers at Chennai (three private and one government). All women underwent an oral glucose tolerance test using 75g glucose load and fasting, 1-h, and 2-h samples were collected. The IADPSG and WHO criteria were compared for diagnosis of GDM. RESULTS: A total of 839 women had GDM by either the IADPSG or the WHO criteria, of whom the IADPSG criteria identified 699 and the WHO criteria also identified 699 women as having GDM. However, only 599/839 women (66.6%) were identified by both criteria. Thus, 140/839 women (16.7%) were missed by both the IADPSG and the WHO criteria. 687/699 (98.2%) of the women with GDM were identified by the WHO criteria. In contrast, each value of IADPSG criteria i.e., fasting, 1 h, and 2 h identified only 12.5%, 14%, and 22%, respectively. CONCLUSIONS: A single WHO cut-point of 2 h > 140 mg/dl appears to be suitable for large-scale screening for GDM in India and other developing countries.