Low risk threshold for acquired diabetogenic factors in Asian Indians

India is facing an epidemic of type 2 diabetes, with high prevalence in urban areas. Urbanisation and associated life style changes adversely affect the risk factors for diabetes unmasking the high genetic tendency existing in the population. Various epidemiological studies in Indians have shown that the increasing prevalence of diabetes could be attributed to a high genetic risk and lower risk thresholds for acquired risk factors such as age, obesity, abdominal adiposity and a high percentage of body fat. Diabetes occurs at a younger age in Indians compared to Whites. The risk of diabetes increases with a body mass index (BMI) of >23 kg/m(2) and waist circumference of 85 cm for men and 80 cm for women in Asian Indians. For a given BMI, Asian Indians have higher central adiposity. There is also evidence of higher insulin resistance amongst Indians, and this is partly explained by higher body fat percentage. A large proportion of urban adults has the metabolic syndrome also which predisposes them to both diabetes and cardiovascular diseases. Recognition of these conditions and institution of early preventive measures are urgently needed.     

Chemical and biological characterization of salmon melanocyte-stimulating hormones

Ten peptides related to melanocyto-stimulating hormone (MSH) have been identified in an acid acetone extract of the chum salmon pituitary. All these peptides are related to the alpha-MSH and beta-MSH families, but no peptide related to gamma-MSH has been found. This result is in accordance with the finding that the gamma-MSH segment is deleted from the N-terminal peptide of salmon pro-opiocortin (NPP I). Based on the structures of newly isolated peptides, the maturation process of MSH is discussed. The major components of salmon MSH were tested for biological activities. In the lipolytic assay with rabbit fat cells, alpha-MSH I and alpha-MSH II were equipotent, but beta-MSH I and NPP I exhibited very low or no activity. On the other hand, the des-acetyl-alpha-MSH I was found to be four times as potent as alpha-MSH I in this assay. The steroidogenic activities of alpha-MSH I and N-des-acetyl-alpha-MSH I were approximately 0.05% of the potency of ovine ACTH. All other peptides exhibited less than 0.01% potency. Salmon alpha-MSHs were found to be somewhat more potent melanophore-stimulating agents than the beta-MSHs.     

High Prevalence of Depressive Symptoms in Patients With Type 1 and Type 2 Diabetes in Developing Countries: Results From the International Diabetes Management Practices Study

OBJECTIVEDepression is common in people with diabetes, but data from developing countries are scarce. We evaluated the prevalence and risk factors for depressive symptoms in patients with diabetes using data from the International Diabetes Management Practices Study (IDMPS).RESEARCH DESIGN AND METHODSIDMPS is an ongoing multinational, cross-sectional study investigating quality of care in patients with diabetes in real-world settings. Data from wave 5 (2011), including 21 countries, were analyzed using the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. Logistic regression analyses were conducted to identify risk factors of depressive symptoms.RESULTSOf 9,865 patients eligible for analysis, 2,280 had type 1 and 7,585 had type 2 diabetes (treatment: oral glucose-lowering drugs [OGLD] only, n = 4,729; OGLDs plus insulin, n = 1,892; insulin only, n = 964). Depressive symptoms (PHQ-9 score ≥5) were reported in 30.7% of those with type 1 diabetes. In patients with type 2 diabetes, the respective figures were 29.0% for OGLDs-only, 36.6% for OGLDs-plus-insulin, and 46.7% for insulin-only subgroups. Moderate depressive symptoms (PHQ-9 score 10–19) were observed in 8–16% of patients with type 1 or type 2 diabetes. Female sex, complications, and low socioeconomic status were independently associated with depressive symptoms. In type 1 diabetes and in the type 2 diabetes OGLDs-only group, depression was associated with poor glycemic control.CONCLUSIONSDepressive symptoms are common in patients with diabetes from developing countries, calling for routine screening, especially in high-risk groups, to reduce the double burden of diabetes and depression and their negative interaction.     

Mutations in K-Ras linked to levels of osteoprotegerin and sensitivity to TRAIL-induced cell death in pancreatic ductal adenocarcinoma cells

Osteoprotegerin (OPG) is a soluble receptor expressed in the serum of patients with diabetes, arthritis and pancreatic cancer. While OPG has been considered a tumor survival factor for bone metastasizing breast and prostate cancers, the role of OPG in pancreatic cancer, which itself rarely metastasizes to bone, is not known. Pancreatic ductal adenocarcinoma (PDAC) cell lines were found to secrete OPG and the level of OPG production correlated with sensitivity to TRAIL-induced apoptosis. Silencing OPG sensitized cells to TRAIL-induced apoptosis. Interestingly, a positive correlation was noted between OPG production level and K-Ras mutation status. Earlier studies implicated K-Ras in conferring resistance to TRAIL-induced apoptosis in pancreatic cells and this study demonstrates that K-Ras mediated TRAIL resistance in pancreatic cancer cells occurs due to increased OPG production. Silencing K-Ras in pancreatic cancer cells decreased OPG levels and increased sensitivity to TRAIL-induced apoptosis. These observations indicate that OPG can play a role in both cell survival and in PDAC cell sensitivity to TRAIL-induced apoptosis, which may contribute to metastasis. Targeted inhibition of OPG binding to TRAIL may represent a therapeutic approach in the treatment of pancreatic cancer.     

Nutritional profile of fibrocalculous pancreatic diabetes and primary forms of diabetes seen in southern India

Plasma levels of retinol binding protein (RBP), prealbumin, total protein, albumin, transferrin and ferritin were estimated in three groups of diabetic patients seen at a diabetes centre in S. India. The groups consisted of patients with fibrocalculous pancreatic diabetes (FCPD), non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). Mean RBP levels were lower in FCPD and IDDM patients compared to controls but this did not reach statistical significance. Prealbumin levels were normal in FCPD patients, but low in IDDM compared to controls (P less than 0.005) and NIDDM (P less than 0.05). FCPD patients had lower transferrin levels compared to controls (P less than 0.05). There were no differences in the levels of total protein, albumin and ferritin in any of the study groups. The study shows that biochemical evidence of undernutrition is seen in FCPD and IDDM patients while NIDDM patients are not significantly different from non-diabetic control subjects.     

Pharmacokinetics of First-Line Antituberculosis Drugs in HIV-Infected Children with Tuberculosis Treated with Intermittent Regimens in India

The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (C_max) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median C_max and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC_0–8]) of INH (C_max, 2.5 versus 5.1 μg/ml, respectively [P = 0.016]; AUC_0–8, 11.1 versus 22.0 μg/ml · h, respectively [P = 0.047[) and PZA (C_max, 34.1 versus 42.3 μg/ml, respectively [P = 0.055]; AUC_0–8, 177.9 versus 221.7 μg/ml · h, respectively [P = 0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median C_max of RMP (1.0 versus 2.8 μg/ml, respectively; P = 0.002) and PZA (31.9 versus 44.4 μg/ml, respectively; P = 0.045) were significantly lower. Among all factors studied, the PZA C_max influenced TB treatment outcome (P = 0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP C_max. The PZA C_max significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.     

Apoptosis in the intestinal epithelium: its relevance in normal and pathophysiological conditions

Apoptosis is now recognized as an important process responsible for maintenance of the cellular balance between proliferation and death. Apoptosis is distinct from necrosis in that it is a programmed form of cell death and occurs without any accompanying inflammation. This form of cell death can be induced by a wide range of cellular signals, which leads to activation of cell death machinery within the cell and is characterized by distinct morphological changes. Apoptosis is especially relevant in the gastrointestinal tract, as the mammalian intestinal mucosa undergoes a process of continual cell turnover that is essential for maintenance of normal function. Cell proliferation is confined to the crypts, while differentiation occurs during a rapid, orderly migration up to the villus. The differentiated enterocytes, which make up the majority of the cells, then undergo a process of programmed cell death (apoptosis). Although apoptosis is essential for the maintenance of normal gut epithelial function, dysregulated apoptosis is seen in a number of pathological conditions in the gastrointestinal tract. The cellular mechanisms regulating this tightly regimented process have not been clearly defined and this topic represents an area of active investigation as delineation of this process will lead to a better understanding of normal gut mucosal growth.