Impact of Type 2 Diabetes Mellitus with a Focus on Asian Indians Living in India and Abroad: A Systematic Review.

BACKGROUND: Diabetes is a highly prevalent disease in the world. Type 2 diabetes mellitus (T2DM) is growing at an alarming rate due to rapid urbanization, migration, aging population, and lifestyle changes. INTRODUCTION: We have summarized the global T2DM distribution in specific International Diabetes Federation (IDF)-defined regions and various countries and highlighted the high risk of T2DM prevalence in Asian Indians living in India and worldwide. METHODS: A systematic review was conducted using combinations of the following key concepts 'T2DM'; 'global distribution'; 'Asian Indians'; 'high risk' and 'prevalence' by searching PubMed and EMBASE databases for articles describing the global distribution of T2DM. From 430 searched articles, 54 full-text articles were reviewed to study the distribution, risk, and prevalence of diabetes in various countries. RESULTS: As per IDF Atlas, 463 million people in 2019 have diabetes worldwide, and it is expected to rise to 700 million by 2045. The global distribution of T2DM differs from various countries to various regions. Asia is the epicenter of diabetes, where 60% of people with diabetes live, mainly in China (139.9 million) and India (65 million). South Asians are more susceptible to developing T2DM as compared to ethnic Europeans. Asian Indians living worldwide are at a high risk of developing T2DM. Those who have migrated to various countries (USA, UK, Australia, Singapore, Mauritius, New Zealand, Fiji, etc.) have a higher prevalence of T2DM than the native population and even more significant than those Indians living in India due to being more insulin resistant. Indians develop T2DM at a younger age and at a lower BMI due to genetic makeup and behavioral and environmental determinants, including diet and sedentary lifestyle and westernization. CONCLUSION: In conclusion, insulin levels were found to be higher not only in adults but also in adolescents and young adults. In addition, rapid urbanization, migration, industrial modernization, and lifestyle changes are other factors responsible for the development of T2DM.

Comparative effect of indomethacin (IndoM) on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in the kidney, small intestine and liver of rats.

Indomethacin (IndoM) has prominent anti-inflammatory and analgesic-antipyretic properties. However, high incidence and severity of side-effects on the structure and functions of the kidney, liver and intestine limits its clinical use. The present study tested the hypothesis that IndoM causes multi-organ toxicity by inducing oxidative stress that alters the structure of various cellular membranes, metabolism and hence functions. The effect of IndoM was determined on the enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in the rat kideny, liver and intestine to understand the mechanism of IndoM induced toxicity. Adult male Wister rats were given IndoM (20 mg/kg) intra-peritoneally in sodium bicarbonate twice a day for 3 d. The body weights of the rats were recorded before and after experimental procedure. IndoM administration significantly increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but inorganic phosphate indicating IndoM induced renal, hepatic and intestinal toxicity. Activity of lactate dehydrogenase along with glucose-6- and fructose-1, 6-bis phosphatase, glucose-6-phosphate dehydrogenase and NADP-malic enzyme increased but malate dehydrogenase decreased in all tissues. Lipid peroxidation (LPO) significantly increased whereas the antioxidant enzymes decreased in all rat tissues studied. The results indicate that IndoM administration caused severe damage to kidney, liver and intestine by icreasing LPO, suppressing antioxidant enzymes and inhibiting oxidative metablolism. The energy dependence was shifted to anaerobic glycolysis due to mitochondrial damage supported by increased gluconeogenesis to provide more glucose to meet energy requirements.

Studies on the effect of sodium arsenate on the enzymes of carbohydrate metabolism, brush border membrane, and oxidative stress in the rat kidney.

Arsenic is an environmental pollutant and its contamination in drinking water poses serious world wide environmental health threats. It produces multiple adverse effects in various tissues, including the kidney. However, biochemical mechanism and renal response to its toxic insult are not completely elucidated. We hypothesized that sodium arsenate (ARS) induces oxidative stress and alters the structure and metabolic functions of kidney. Male Wistar rats were administered ARS (10 mg/kg body weight/day), intraperitoneally daily for 10 days. ARS administration increased blood urea nitrogen, serum creatinine, cholesterol, glucose, and phospholipids but decreased inorganic phosphate, indicating kidney toxicity. The activity of brush border membrane (BBM) enzymes significantly lowered in both cortex and medulla. Activity of hexokinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenases, and NADP-malic enzyme significantly increased whereas malate dehydrogenase, glucose-6-phosphatase, and fructose 1,6 bis phosphatase decreased by ARS exposure. The activity of superoxide dismutase, GSH-peroxidase, and catalase were selectively altered in renal tissues along with an increase in lipid peroxidation. The present results indicated that ARS induced oxidative stress caused severe renal damage that resulted in altered levels of carbohydrate metabolism and BBM enzymes.

Effect of uranyl nitrate on enzymes of carbohydrate metabolism and brush border membrane in different kidney tissues.

Uranium, the heaviest of the naturally occurring elements is widely present as environmental contaminant from natural deposits, industrial emissions and most importantly from modern weapons. Histopathological examinations revealed that uranyl nitrate (UN) exposure caused severe damage to pars recta of renal proximal tubule. However, biochemical events involved in cellular response to renal injury are not completely elucidated. We hypothesized that UN exposure would severely damage kidney tissues and alter their metabolic functions. Rats were treated with a single nephrotoxic dose of UN (0.5mg/kg body weight) i.p. After 5d, effect of UN was studied on the activities of various enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in different kidney tissues. Activity of lactate dehydrogenase increased whereas activities of isocitrate, succinate and malate dehydrogenases, glucose-6-phosphatase and fructose-1,6-bisphosphatase significantly decreased by UN exposure. Activity of glucose-6-phosphate dehydrogenase decreased whereas that of NADP-malic enzyme increased. The activities of BBM enzymes were significantly lowered and after dissociation from BBM excreted in urine. Lipid peroxidation and the activities of superoxide dismutase and glutathione peroxidase increased whereas catalase activity decreased by UN. UN treatment caused specific alterations in the activities of metabolic and membrane enzymes and perturbed antioxidant defenses.

Influence of Ramadan-type fasting on carbohydrate metabolism, brush border membrane enzymes and phosphate transport in rat kidney used as a model.

Ramadan fasting is a unique model of fasting in which Muslims the world over abstain from food and water from dawn to sunset for 1 month. We hypothesized that this model of prolonged intermittent fasting would result in specific adaptive alterations in rat kidney to keep a positive balance of metabolites and inorganic phosphate (Pi). The effect of Ramadan-type fasting was studied on enzymes of carbohydrate metabolism and brush border membrane (BBM) and BBM uptake of 32Pi in different renal tissue zones in the rat model. Rats were fasted (12 h) and then re-fed (12 h) daily for 30 d similar to human Ramadan fasting. Ramadan-type fasting resulted in increased serum Pi and phospholipids, whereas Pi clearance decreased. Serum creatinine and its clearance were not affected. Fasting caused a significant decrease in the activities of lactate and malate dehydrogenases, glucose-6-phosphatase and fructose-1,6-bisphosphatase, both in the renal cortex and medulla. However, the activity of glucose-6-phosphate dehydrogenase profoundly increased but that of malic enzyme decreased. The activities of alkaline phosphatase and gamma-glutamyl transpeptidase in BBM decreased, whereas transport of 32Pi significantly increased. The decrease in enzyme activities and increase in 32Pi transport were due to alterations of both maximal velocities and relative affinities. The results indicate that Ramadan-type fasting caused specific metabolic alterations with enhanced Pi conservation in different kidney tissues in a rat model used for Ramadan fasting in man.

Influence of green tea on enzymes of carbohydrate metabolism, antioxidant defense, and plasma membrane in rat tissues.

OBJECTIVE: Green tea, consumed worldwide since ancient times, is considered beneficial to human health. We hypothesized that green tea would enhance antioxidant defenses and specific metabolic activities of rat intestine, liver, and kidney to improve their functions. METHODS: The effect of green tea given to rats in the diet or drinking water for 25 d was determined on blood chemistry and on activities of enzymes of carbohydrate metabolism, brush border membrane, and antioxidant defense. RESULTS: Serum glucose, cholesterol, phosphate, and body weight decreased, whereas the activities of lactate and malate dehydrogenases and glucose-6- and fructose 1,6-bis-phosphatases increased in the intestine and kidney but slightly changed in the liver. Activity of glucose-6-phosphate dehydrogenase profoundly increased in the renal cortex but decreased in other tissues. Lipid peroxidation increased in the intestine and renal medulla and decreased in the renal cortex and liver; catalase increased in all tissues but the medulla. Superoxide dismutase activity decreased in the intestine but increased in renal tissues. Activities of brush border membrane enzymes in general increased in the intestine and kidney. CONCLUSION: Green tea consumption resulted in enhanced enzyme activities of carbohydrate metabolism and antioxidant defenses, which may lead to improved health.

Influence of Ramadan-type fasting on enzymes of carbohydrate metabolism and brush border membrane in small intestine and liver of rat used as a model.

During Ramadan, Muslims the world over abstain from food and water from dawn to sunset for a month. We hypothesised that this unique model of prolonged intermittent fasting would result in specific intestinal and liver metabolic adaptations and hence alter metabolic activities. The effect of Ramadan-type fasting was studied on enzymes of carbohydrate metabolism and the brush border membrane of intestine and liver from rat used as a model. Rats were fasted (12 h) and then refed (12 h) daily for 30 d, as practised by Muslims during Ramadan. Ramadan-type fasting caused a significant decline in serum glucose, cholesterol and lactate dehydrogenase activity, whereas inorganic phosphate increased but blood urea N was not changed. Fasting resulted in increased activities of intestinal lactate (+34%), isocitrate (+63%), succinate (+83%) and malate (+106%) dehydrogenases, fructose 1,6-bisphosphatase (+17%) and glucose-6-phosphatase (+22%). Liver lactate dehydrogenase, malate dehydrogenase, glucose-6-phosphatase and fructose 1,6-bisphosphatase activities were also enhanced. However, the activities of glucose-6-phosphate dehydrogenase and malic enzyme fell significantly in the intestine but increased in liver. Although the activities of alkaline phosphatase, gamma-glutamyl transpeptidase and sucrase decreased in mucosal homogenates and brush border membrane, those of liver alkaline phosphatase, gamma-glutamyl transpeptidase and leucine aminopeptidase significantly increased. These changes were due to a respective decrease and increase of the maximal velocities of the enzyme reactions. Ramadan-type fasting caused similar effects whether the rats fasted with a daytime or night-time feeding schedule. The present results show a tremendous adaptation capacity of both liver and intestinal metabolic activities with Ramadan-type fasting in rats used as a model for Ramadan fasting in people.

Effect of cisplatin on renal brush border membrane enzymes and phosphate transport.

Cisplatin (CDDP) is widely used in the treatment of various cancers but its clinical use is associated with dose limiting nephrotoxicity. The present work was carried out to study the effect of administration of CDDP on rat renal brush border membrane (BBM) marker enzymes and inorganic phosphate (Pi) transport across BBM vesicles (BBMV). Animals were administered a single intraperitoneal dose of CDDP (6 mg/kg body weight) or normal saline and then sacrificed 2, 4, 8 and 16 days after this treatment. The administration of CDDP resulted in increased serum creatinine and blood urea nitrogen levels and decreased activity of BBM marker enzymes in the BBM as well as in the homogenates of cortex and medulla. Kinetic studies showed that the Vmax of the enzymes was decreased in BBM from CDDP treated rats while the Km remained unchanged. The Na+ -gradient dependent transport of Pi across BBMV was also significantly reduced after CDDP treatment. These results strongly suggest that the administration of a single nephrotoxic dose of CDDP results in impairment of the functions of renal BBM.