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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythrocyte glucose consumption in red blood cells from healthy donors or insulin-dependent diabetics with stable glycemia was measured using the 2-deoxyglucose technique. Data showed that the formation of glucose-6P was severely impaired in diabetic red blood cells in both normo- and hyperglycemic incubation conditions. This defect seems to be inherent to the disease. Coincubation with Metformin (6.4 ug/ml) did not modify the G6P levels in RBCs from healthy donors and in RBCs from diabetics when incubated in normoglycemic conditions. However, when diabetics RBCs were incubated in a hyperglycemic medium, addition of Metformin strongly improved the intracellular levels of G6P. The underlying mechanism for the defect and the correction by Metformin remains to be determined. This study shows that also red blood cells may be involved in the failure of glucose homeostasis in diabetes and thus this may represent an additional target for therapy.
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PMID:Erythrocyte glucose consumption in insulin-dependent diabetes: effect of metformin in vitro. 193 70

Metformin, glibenclamide and their combination were compared in a randomized, double-blind trial in patients with non-insulin-dependent diabetes mellitus (NIDDM) using a parallel group design. The study was performed in primary health care, and the purpose was to assess possible synergistic effects of combination therapy with the two drugs as primary treatment versus conventional oral therapy, starting with one drug and adding the other, if necessary. Lipids and lipoproteins were measured in the study, and preliminary results are reported for one hundred sixteen patients concluding 6 months maintenance therapy. Comparison of mean differences showed that patients randomized to combination therapy (n = 60) demonstrated a greater decrease in total- and LDL-cholesterol levels after 4 and 6 months treatment than patients randomized to conventional therapy starting with either metformin (n = 28) or glibenclamide (n = 28). For LDL-cholesterol a significant difference was also found between patients solely on monotherapy with lower values after treatment with metformin. Triglycerides did not change significantly, and only minor fluctuations were seen in HDL-cholesterol, independent of treatment. Obese patients had significantly higher triglyceride concentrations than the non-obese group, both at baseline and after treatment, as well as significantly lower HDL-cholesterol levels. The mean triglyceride concentration (+/- SD) after 6 months treatment was 2.32 +/- 1.38 mmol/l in the obese group (n = 69) and 1.54 +/- 0.84 mmol/l in non-obese (n = 47). For HDL-cholesterol the corresponding values were 0.83 +/- 0.23 mmol/l in obese and 0.93 +/- 0.29 mmol/l in non-obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of metformin and glibenclamide alone and in combination on serum lipids and lipoproteins in patients with non-insulin-dependent diabetes mellitus. 193 72

Metformin and glibenclamide were compared in a randomized, double-blind trial in patients with non-insulin-dependent diabetes mellitus (NIDDM) using a parallel group design. The study was performed in primary health care, and the main purpose was to assess combination therapy with the two drugs as primary treatment versus conventional oral therapy. After a 2 months diet period patients were randomized to commence treatment with either metformin, glibenclamide or the combination of both. Patients randomized to monotherapy received the alternative drug in addition if the maximal dose i.e. 3 g metformin or 14 mg glibenclamide was insufficient to normalize the fasting blood glucose concentration (FBG). Randomization and dose escalation occurred at FBG greater than or equal to 6.7 mmol/l. The titrated dose was continued for 6 months, whereafter placebo was given for 2 weeks. Seventy-two patients were randomized to either the metformin group (n = 38) or the glibenclamide group (n = 34). Fifty-six completed 6 months treatment, twenty-eight in each randomized group. Glycaemic control was unchanged after diet alone in all groups. The improvement during drug treatment was highly significant (p less than 0.001), mean FBG difference (+/- SEM) 3.2 +/- 0.4 mmol/l and mean HbA1c difference (+/- SEM) 1.5 +/- 0.2% (n = 56). There were no significant differences between patients treated solely with metformin (n = 16) and glibenclamide (n = 17) or between patients treated with a combination of glibenclamide added to metformin (n = 12) and metformin added to glibenclamide (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative efficacy of metformin and glibenclamide in patients with non-insulin-dependent diabetes mellitus. 193 77

The mechanism (both at the whole body and cellular level) by which metformin improves insulin sensitivity has yet to be defined. In the present study, we examined in vivo insulin-mediated whole-body glucose disposal, glycogen synthesis, hepatic glucose production, and insulin secretion, as well as in vitro muscle insulin receptor tyrosine kinase activity in eight control, eight neonatal streptozotocin diabetic rats, and eight diabetic rats before and after treatment with metformin. Ten weeks after birth diabetic rats had higher fasting (132 + 5 v 101 + 2 mg/dL) and postmeal (231 + 10 v 133 + 3) plasma glucose levels compared with controls (P less than .001). Metformin treatment was followed by a significant decrease in the growth rate and normalized glucose tolerance without enhancing the deficient insulin response. Insulin-mediated glucose uptake in diabetic versus control rats was reduced (P less than .01) during the high-dose (15.4 + 0.6 v 18.3 + 1.0 mg/kg.min) insulin clamp study and was increased to values greater (P less than .05) than controls following metformin treatment. Muscle glycogen synthetic rate in vivo, measured by incorporation of 3H-3-glucose radioactivity, was diminished by 25% (P less than .01) in diabetic rats, restored to normal values with metformin, and correlated closely (r = .82, P less than .002) with total-body glucose uptake during the insulin clamp in all three groups. Insulin receptor tyrosine kinase activity, measured in partially purified insulin receptors, was reduced in diabetic rats and increased to supernormal levels after metformin. The decrease in muscle tyrosine kinase activity in diabetic versus control animals was entirely accounted for by a reduction in maximal velocity (Vmax) (32 v 45 pmol/mg.min, P less than .01) and increased to supernormal levels following metformin (91 pmol/mg.min, P less than .001) without any change in affinity (Km). Muscle tyrosine kinase activity was closely correlated with both the muscle glycogen synthetic rate (r = .82, P less than .002) and total-body insulin-mediated glucose disposal (r = .64, P less than .01) in vivo. The close correlation between in vivo insulin action, muscle glycogen synthesis, and muscle insulin receptor tyrosine kinase activity is consistent with an important role of the enzyme in the insulin resistance of diabetes and its improvement following metformin treatment.
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PMID:Effect of metformin treatment on insulin action in diabetic rats: in vivo and in vitro correlations. 215 41

Nineteen obese patients with Type 2 diabetes mellitus were treated for periods of 3 months with placebo, guar gum (5 g three times daily) and metformin (500 mg three times daily) in a randomized double-blind, double-placebo, cross-over study. Both active agents decreased fasting blood glucose from 11.4 +/- 3.7 mmol l-1 (mean +/- SD) to 8.6 +/- 2.8 mmol l-1 on metformin (p less than 0.001) and to 9.5 +/- 3.9 mmol l-1 on guar gum (p less than 0.01). Metformin significantly reduced the very low density lipoprotein (VLDL) cholesterol concentration from 0.62 (+0.73, -0.34) mmol l-1 (geometric mean (+SD, -SD)) to 0.43 (+0.58, -0.25) mmol l-1, (p less than 0.02), but unless hyperlipidaemia was present there were no changes in other serum lipid or lipoprotein levels. In patients with serum cholesterol greater than 6.5 mmol l-1 decreases in serum triglycerides from 3.29 (+3.27, -1.64) to 2.46 (+2.55, -1.25) mmol l-1 (p less than 0.02) occurred with metformin. In these patients guar gum produced a reduction in serum cholesterol (from 7.70 +/- 0.90 to 6.41 +/- 1.11 mmol l-1, p less than 0.01) due to an effect on low density lipoproteins. These differential effects may be important in planning therapy when hyperlipidaemia accompanies Type 2 diabetes.
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PMID:Placebo-controlled trial of the effects of guar gum and metformin on fasting blood glucose and serum lipids in obese, type 2 diabetic patients. 215 10

Metformin is a hypoglycemic drug effective in the treatment of non-insulin-dependent diabetes mellitus and increasingly used in Canada and Europe. Effects on intestinal glucose absorption, insulin secretion, and hepatic glucose production are insufficient to explain its hypoglycemic action, with most evidence suggesting that the major effect of the drug is on glucose utilization. In vivo and in vitro studies have demonstrated that metformin stimulates the insulin-induced component of glucose uptake into skeletal muscle and adipocytes in both diabetic individuals and animal models. This increase is more significant in diabetic than in nondiabetic animals, suggesting an enhanced action of the drug in the hyperglycemic state. The increase in glucose uptake is also reflected in an increase in the insulin-dependent portion of glucose oxidation. Potential sites of action of metformin are the insulin receptor and the glucose transporters. Although metformin increases insulin binding in various cell types, this effect is not universal and does not correlate with stimulation of glucose utilization. In contrast, direct effects of the drug on the glucose-transport system have been demonstrated. Metformin elevates the uptake of nonmetabolizable analogues of glucose in both nondiabetic rat adipocytes and diabetic mouse muscle. In the latter, the stimulatory effect of the drug is additive to that of insulin. In human and rat muscle cells in culture, metformin increases glucose-analogue transport independently of and additive to insulin, suggesting an insulin-dependent action. Most of these results suggest that the basis for the hypoglycemic effect of this biguanide is probably at the level of skeletal muscle by increasing glucose transport across the cell membrane.
Diabetes Care 1990 Jun
PMID:Cellular mechanism of action of metformin. 216 56

This study investigated the relative effect of obesity alone and in combination with non-insulin-dependent diabetes mellitus (NIDDM) on the intracellular processing of insulin and evaluated the effect of metformin therapy on this process. Monocytes from 11 obese hyperinsulinemic subjects, 13 obese hyperinsulinemic NIDDM patients, and 7 nondiabetic control subjects were incubated with A14-125I-labeled insulin for 60 min at 37 degrees C, and intracellular insulin degradation was characterized by high-performance liquid chromatography. Total cell-associated insulin (insulin binding) and internalized and degraded insulin were decreased in obese subjects and significantly decreased in obese NIDDM patients compared with nondiabetic control subjects. In NIDDM patients, intracellular insulin degradation was inversely correlated with fasting plasma glucose (P less than 0.01). Eight obese subjects and 9 obese NIDDM patients were restudied after 4 wk of therapy with metformin (850 mg twice a day). Plasma levels of the drug were superimposable in the two groups. Metformin therapy did not change glucose and insulin levels in obese subjects but caused a decrease in blood glucose in obese NIDDM patients. Total cell-associated radioactivity (insulin binding) significantly increased in both groups (P less than 0.01). On the contrary, internalized radioactivity increased (0.83 +/- 0.3 vs. 1.31 +/- 0.35%, P less than 0.01), and similarly, insulin degradation was enhanced (54.6 +/- 8.9 vs. 74.22 +/- 9.15%, P less than 0.01) only in monocytes from obese NIDDM patients. However, the levels of these parameters were still lower than in control subjects (internalization, 2.94 +/- 0.68%; degradation, 93.03 +/- 3.7%).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Jul
PMID:Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients. 219 88

Platelet density profiles, intraplatelet nucleotides, intraplatelet beta thromboglobulin (beta TG), plasma beta TG levels, intraplatelet cyclic AMP (cAMP) levels, platelet release reaction, platelet thromboxane (TX)B2 production and plasma fibrinogen levels were investigated in 24 newly diagnosed, non-insulin-dependent diabetic patients and 12 comparable controls. These variables were measured at diagnosis, after a 3-6 week dietary run-in period, and again after 6 months on treatment with either metformin or gliclazide therapy. With dietary restriction of refined carbohydrate and oral hypoglycaemic therapy, there was a reduction in platelet density (p less than 0.05), intraplatelet nucleotides (p less than 0.001), intraplatelet beta TG (p less than 0.001), plasma beta TG (p less than 0.001) and there was an increase in intraplatelet cAMP levels (p less than 0.05). Although these platelet variables returned towards normal, only the platelet density mean returned to within the normal range. There was no significant change in the platelet TXB2 production and plasma fibrinogen levels with treatment. Metformin and gliclazide were equally effective in the glycaemic control of non-insulin-dependent diabetes, and there was no difference between the platelet variables measured in the two groups. We would therefore suggest that improvement of glycaemic control, rather than any specific effect of the oral hypoglycaemic agent employed, is the most important factor in returning these parameters towards normality.
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PMID:Effect of glycaemic control, metformin and gliclazide on platelet density and aggregability in recently diagnosed type 2 (non-insulin-dependent) diabetic patients. 253 84

The role of metformin on platelet aggregation was studied in subjects affected by relatively well controlled type 1 diabetes. 1700 mg of metformin were added to their usual daily treatment; nothing else was changed. Patients were trained to monitor their own glycaemia and presence of degenerative retinopathy was proved. Before the administration of metformin and on day 21, the platelet induced by 1.25, 2.5 and 5 mumol of ADP and by collagen was studied. Fibrinogen, cholesterol, triglycerides, glycosylated haemoglobin and mean blood glucose levels did not show any significant modification after treatment but the maximum aggregation induced by ADP was significantly decreased; the inhibition of aggregation was particularly sensitive for low doses of ADP. No significant correlation was found between the variations in metabolism data and the reduction of the amplitude of platelet aggregation. Metformin, added to the usual treatment undergone by a diabetic treated with insulin, seems to affect platelet aggregation independently of other metabolic factors.
Diabetes Res Clin Pract 1989 Jan 03
PMID:Study of the effect of metformin on platelet aggregation in insulin-dependent diabetics. 270 18

Type B lactic acidosis, or pathological hyperlactatemia (PHL), is defined by an arterial lactate level greater than 5 mmol X l-1. It is a known and severe complication of diabetes mellitus treated with biguanide hypoglycaemic agents, particularly phenformin which was taken off the French pharmaceutical market in 1977. Metformin, which remains the only biguanide hypoglycaemic agent currently prescribed in France, may also lead to this complication. However it does so less frequently and mostly in the diabetic presenting with renal failure. A few well studied cases showed that PHL could be correlated with excessive metformin blood levels, i.e. a toxic mechanism. In order to find out whether this toxic mechanism was the real cause of PHL in diabetics treated with metformin, a systematic study of metformin blood levels was carried out in 20 such patients. They had all been admitted to a critical care unit presenting with PHL. The results of this study led us to distinguish between two groups of patients. The seven patients of the first group had high metformin blood levels (4.3 to 65.8 micrograms X l-1). In these, renal excretion or extrarenal dialysis lowered or normalized their hyperlactatemia, and six of the seven recovered from PHL. In the second group, with thirteen patients, metformin blood levels were within the normal therapeutic range (0.225 to 3 micrograms X l-1) for seven patients and close to zero for the other six. This second group received the same treatment as the first one. Only three patients recovered, the others all died.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Physiopathological approach to pathological hyperlactatemia in the diabetic patient. Value of blood metformin]. 310 85


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