Hyperglycemia In Diabetic Subjects Research Articles

Somogyi Effect in a Patient of Type 2 Diabetes Mellitus

Morning hyperglycemia in diabetic subjects may be caused by the dawn phenomenon, or the Somogyi effect, or poor glycemic control. The dawn phenomenon is a normal rise in blood sugar as a person’s body prepares to wake up. In the early morning hours, hormones (growth hormone, cortisol and catecholamines) cause the liver to release large amounts of sugar into the bloodstream. For most people, the body produces insulin to control the rise in blood sugar. If the blood sugar level drops too low in the early morning hours, hormones (such as growth hormone, cortisol, and catecholamines) are released. These help reverse the low blood sugar level but may lead to blood sugar levels that are higher than normal in the morning. If the body doesn’t produce enough insulin, blood sugar levels can rise. This may cause high blood sugar in the morning (before eating). Somogyi effect occurs in a person who takes insulin doesn’t eat a regular bedtime snack, and the person’s blood sugar level drops during the night. The person’s body responds to the low blood sugar by releasing hormones that raise the blood sugar level. This may cause a high blood sugar level in the early morning. The dawn phenomenon is more common than the Somogyi effect. To diagnose these phenomena, it is useful to measure plasma glucose levels for several nights between 2 a.m. and 5 a.m. or use a continuous glucose monitoring system.

Erratum to: A review of α-amylase inhibitors on weight loss and glycemic control in pathological state such as obesity and diabetes

Overweight, obesity, and diabetes are the most common disorders in the world. In most diets, carbohydrates are the greatest source of calories. Inhibition of carbohydrate digestion or absorption can decrease calorie intake to promote weight loss and combat obesity. It is also a mechanism for reducing hyperglycemia in diabetic subjects. Before being absorbed by the body, carbohydrates must be broken down into monosaccharides. α-Amylase catalyzes the hydrolysis of α-(1,4)-d-glycosidic linkages of starch and other glucose polymers. Inhibitors of this enzyme can be used in treatment of obesity and diabetes. In diabetic patients, inhibition of α-amylase leads to prohibition starch breaking and results in lower levels of blood glucose. The effects of pseudosaccharides, proteinaceous, and polyphenolic inhibitors have been previously reported. Polyphenolic compounds are widely distributed in plants and fruits and are present in normal diets. These compounds have been shown to possess beneficial effects in diabetes, cardiovascular diseases, atherosclerosis, allergy, inflammation, and osteoporosis. Among polyphenolic compounds, flavonoids are of particular significance: They have been shown to reduce cholesterol synthesis via direct action on HMG-CoA reductase and hydrolyze lipids via inhibition of phosphodiesterase (PDE) and diminution of cAMP breakdown. In recent years, many lines of research have been done on those plants which are being used traditionally as drug plants, and their effects have been surveyed on weight loss and control of blood glucose levels in diabetic patients. In this review, we want to investigate α-amylase inhibitors especially human pancreatic α-amylase (HPA)

Pharmacodynamics and Subchronic Toxicity in Mice and Monkeys of ISIS 388626, a Second-Generation Antisense Oligonucleotide That Targets Human Sodium Glucose Cotransporter 2

ISIS 388626, a 2'-methoxyethyl (MOE)-modified antisense oligonucleotide (ASO) that targets human sodium glucose cotransporter 2 (SGLT2) mRNA, is in clinical trials for the management of diabetes. SGLT2 plays a pivotal role in renal glucose reabsorption, and inhibition of SGLT2 is anticipated to reduce hyperglycemia in diabetic subjects by increasing urinary glucose elimination. To selectively inhibit SGLT2 in the kidney, ISIS 388626 was designed as a "shortmer" ASO, consisting of only 12 nucleotides with two 2'-MOE-modified nucleotides at the termini. Mice and monkeys received up to 30 mg/kg/week ISIS 388626 via subcutaneous injection for 6 or 13 weeks. Dose-dependent decreases in renal SGLT2 mRNA expression were observed, which correlated with dose-related increases in glucosuria without concomitant hypoglycemia. There were no histologic changes in the kidney attributed to SGLT2 inhibition after 6 or 13 weeks of treatment. The remaining changes observed in these studies were typical of those produced in these species by the administration of oligonucleotides, correlated with high doses of ISIS 388626, and were unrelated to the inhibition of SGLT2 expression. The kidney contained the highest concentration of ISIS 388626, and dose-dependent basophilic granule accumulation in tubular epithelial cells of the kidney, which is evidence of oligonucleotide accumulation in these cells, was the only histologic change identified. No changes in kidney function were observed. These results revealed only readily reversible changes after the administration of ISIS 388626 and support the continued investigation of the safety and efficacy of ISIS 388626 in human trials.

The antidiabetic metformin is toxic to liver mitochondria of Zucker Diabetic Fatty (ZDF) rats: a cellular metabolomic study with 13C‐lactate and carbon 13 NMR

Metformin decreases hyperglycemia in diabetic subjects and animals. This effect results in part from the inhibition of hepatic gluconeogenesis. The objective of this study was to investigate in vitro the effect of metformin on hepatic lactate gluconeogenesis by using an innovative approach.Precision‐cut liver slices from adult male ZDF rats were incubated with variously 13C‐labeled lactates (5 mM) or with 5 mM unlabeled lactate plus 25 mM 13C‐bicarbonate. Substrate removal and product formation were measured by enzymatic and 13C‐NMR methods.In slices from fasted lean ZDF rats, metformin dose‐dependently inhibited 13C‐glucose synthesis from [2‐13C]‐lactate (IC50 2.3 mM). The labeling patterns of the glucoses synthesized indicated that lactate gluconeogenesis involved not only the passage of carbons through pyruvate carboxylase and the reversible equilibration of oxaloacetate with fumarate but also the entire tricarboxylic acid cycle.In slices from fed diabetic ZDF rats, 2 mM metformin inhibited lactate consumption, glucose production, the synthesis of all the 13C‐labeled glucose carbons, the production of 13CO2 and reduced the cellular ATP level. By contrast, metformin dramatically increased lactic acid production and ketogenesis.These results strongly suggest that a compound found to be toxic to liver mitochondria in vitro should not necessarily be withdrawn from drug development.

Investigation of an Amylase Inhibitor on Human Glucose Absorption after Starch Consumption

Inhibition of carbohydrate metabolism or absorption can decrease calorie intake to promote weight loss and combat obesity. It is also a mechanism for reducing hyperglycemia in diabetic subjects. A concentrated northern kidney bean extract was found to be an effective in vitro amylase inhibitor, thus potentially affecting the absorption of starch carbohydrates. This product was tested in two single dose human studies. Eleven fasting subjects were given 4 slices of white bread and 42 g of margarine with or without 1.5 g of bean extract. Absorption as measured by the area under the plasma glucose-time curve was inhibited 66%. A full meal study with 7 subjects and 0.75 g of extract caused a non-significant 28-41% reduction in absorption. There was a dose-response decrease in glucose absorption by the extract. The bean extract has in vivo efficacy for inhibition of starch absorption and may prove beneficial in weight reduction in individuals consuming large amounts of starch. It also may inhibit starch-induced hyperglycemia in normal and diabetic subjects.

A semiclosed-loop optimal control system for blood glucose level in diabetics

In this manuscript, the well-known Bergman nonlinear mathematical model of the plasma glucose/insulin interaction is adopted and a semi closed-loop optimal technique is proposed for the correction of hyperglycemia in diabetic subjects. Computer simulations are used to evaluate the effectiveness of the proposed technique and to demonstrate its superiority in controlling hyperglycemia over other existing algorithms.

Evidence for decreased splanchnic glucose uptake after oral glucose administration in non-insulin-dependent diabetes mellitus.

The role of splanchnic glucose uptake (SGU) after oral glucose administration as a potential factor contributing to postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) has not been established conclusively. Therefore, we investigated SGU in six patients with NIDDM and six weight-matched control subjects by means of the hepatic vein catheterization (HVC) technique. In a second part, we examined the applicability of the recently developed OG-CLAMP technique in NIDDM by comparing SGU and first-pass SGU during HVC with SGU during the OG-CLAMP experiment. The OG-CLAMP method combines a euglycemic, hyperinsulinemic clamp and an oral glucose tolerance test (75 g) during steady state glucose infusion (GINF). During HVC, SGU equals the splanchnic fractional extraction times the total (oral and arterial) glucose load presented to the liver. For OG-CLAMP, SGU was calculated as first-pass SGU by subtracting the integrated decrease in GINF over 180 min from 75 g. Cumulative splanchnic glucose output after oral glucose correlated significantly between both methods and was increased significantly in NIDDM patients (73.1+/-5.1 g for HVC, 76.5+/-5.5 for OG-CLAMP) compared with nondiabetic patients (46.7+/-4.4 g for HVC, 57.5+/-1.9 for OG-CLAMP). Thus, in NIDDM patients, SGU (7.4+/-2.1 vs. 37.8+/-5.9% in nondiabetic patients, P < 0.001) and first-pass SGU (4.7+/-1.7 vs. 26.5+/-5.1% in nondiabetic patients, P < 0.01) were decreased significantly during HVC, as was SGU during OG-CLAMP (3.9+/-1.7 vs. 23.4+/-2.5% in nondiabetic patients, P < 0.0001). SGU measured during OG-CLAMP correlated significantly with SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.94, P < 0.01 for nondiabetic patients) and first-pass SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.84, P < 0.05 for nondiabetic patients) during HVC. In conclusion, (a) SGU after oral glucose administration is decreased in NIDDM as measured by both methods, and (b) SGU during the OG-CLAMP is well-correlated to SGU and first-pass SGU during HVC in NIDDM. The decrease in SGU in NIDDM might contribute to postprandial hyperglycemia in diabetic subjects.