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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impairment in pancreatic production of insulin, a cardinal feature of noninsulin dependent diabetes mellitus (NIDDM), was quantified and the kinetics of insulin secretion characterized in six obese individuals with NIDDM before and after weight loss (18.0 +/- 3.0 kg, mean +/- SEM) using a validated mathematical model that employs C-peptide as a marker of the in vivo rate of insulin secretion. The metabolic clearance of C-peptide, assessed by decay analysis after bolus injection of biosynthetic human C-peptide, was not changed by weight loss (0.143 +/- 0.009 L/min.m2 vs. 0.137 +/- 0.010 L/min.m2). Kinetic parameters from each individual's decay curve before and after weight loss were used to derive accurate rates of secretion during the basal (postabsorptive) state, an oral glucose tolerance test and two hyperglycemic clamps. Basal rates of insulin secretion declined 20 +/- 5 pmol/min.m2 (96 +/- 15 to 76 +/- 15 pmol/min.m2, P less than 0.05) concomitant with decreases of 6.9 +/- 0.9 mmol/L in fasting serum glucose (13.7 +/- 1.0 to 6.8 +/- 0.7 mmol/L, P less than 0.05), 60 +/- 14 pmol/L in serum insulin (134 +/- 30 to 74 +/- 15 pmol/L, P less than 0.05), and 0.15 +/- 0.03 pmol/ml in plasma C-peptide (0.67 +/- 0.11 to 0.52 +/- 0.08 pmol/ml, P less than 0.05) concentrations. As expected, weight loss resulted in improved glucose tolerance as measured by the glycemic profiles during the oral glucose tolerance test (P less than 0.05 analysis of variance). The insulin secretory response before weight loss showed a markedly reduced ability to respond appropriately to an increase in the ambient serum glucose. After weight loss, the pancreatic response was more dynamic (P less than 0.05, analysis of variance) and parralleled the moment-to-moment changes in glycemia. Insulin production above basal doubled (11.2 +/- 3.2 to 24.5 +/- 5.8 nmol/6h.m2, P less than 0.05) and peak rates of insulin secretion above basal tripled (55 +/- 16 to 157 +/- 32 pmol/min/m2, P less than 0.05). To assess the beta-cell response to glucose per se and the changes associated with weight reduction, two hyperglycemic clamps were performed at steady state glucose levels in the range characteristic of individuals with severe NIDDM. At a fixed glycemia of 20 mmol/L, average rates of insulin secretion increased almost 2-fold with treatment (161 +/- 41 to 277 +/- 60 pmol/min.m2, P less than 0.05). At an increment of 6 mmol/L glucose above prevailing fasting glucose levels, the average rate of insulin secretion increased 53% (120 +/- 21 to 183 +/- 39 pmol/min.m2, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of weight loss and reduced hyperglycemia on the kinetics of insulin secretion in obese non-insulin dependent diabetes mellitus. 218 85

Combination sulfonylurea-insulin therapy for patients with diabetes mellitus has been evaluated by numerous investigators with various experimental designs. Much of the data are conflicting, and clear conclusions do not seem justified. Insulin-sulfonylurea therapy is probably not clinically useful in most patients with insulin-dependent diabetes mellitus. Most non-insulin-dependent diabetic (NIDDM) patients are also unlikely to have meaningful improvement in glycemic regulation on insulin-sulfonylurea therapy. A subset of NIDDM patients who are mildly to moderately obese, have adequate endogenous insulin secretory reserve, and are in poor glycemic regulation (fasting plasma glucose greater than 11 mM and/or HbA1 greater than 10%), despite twice-daily insulin administration of greater than 70 U/day, may show significant improvement of glycemic regulation and/or decreases in insulin daily dose on insulin-sulfonylurea therapy. The mechanisms by which insulin-sulfonylurea therapy improves glycemic regulation and decreases insulin requirements involve an increase in endogenous insulin secretion and possibly some extrapancreatic actions of the sulfonylureas on muscle and liver.
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PMID:Combination insulin-sulfonylurea therapy. 219 50

Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low-density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60-400) and 131I-labeled VLDL2 (Sf 20-60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P less than 0.01). VLDL2 was less affected (19% reduction, P less than 0.05), IDL was unchanged, and LDL fell 17% (P less than 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1-apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P less than 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P less than 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy.
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PMID:Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. 220 Jul 27

To determine the contribution of skeletal muscle to fasting hyperglycemia in noninsulin dependent type II diabetes (NIDDM), the forearm balance of glucose, lactate, and alanine was quantified in 25 control subjects, 21 hyperglycemic (blood glucose: 11.6 mmol/L), and 19 insulin-treated patients with NIDDM (blood glucose: 5.8 mmol/L). Forearm glucose uptake was similar in controls (4.6 +/- 0.6 mumol L-1 min-1) and in hyperglycemic diabetic patients (4.5 +/- 0.9 mumol L-1 min-1). In spite of this, in the diabetic patients lactate (5.1 +/- 0.8 mumol L-1 min-1) and alanine (2.6 +/- 0.4) release by the forearm was 3- and 2-fold higher than in the control group (lactate: 1.7 +/- 0.8, P less than 0.005; and alanine: 1.3 +/- 0.2, P less than 0.05, respectively). The ratio of lactate release to glucose uptake was 57% and 18% in diabetic and control subjects, respectively. Insulin administration did not affect either glucose uptake or the release of gluconeogenic substrates by the forearm. It is concluded that: 1) in fasting patients with NIDDM, glucose is taken up by the skeletal muscle in normal amounts but preferentially used nonoxidatively with lactate formation. This suggests that, although the muscle does not contribute directly to fasting hyperglycemia, it may play an indirect role through an increased delivery of glucose precursors; and 2) insulin-induced normoglycemia is maintained by mechanisms that do not involve the exchange of glucose and gluconeogenic substrates by the skeletal muscle.
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PMID:Glucose and gluconeogenic substrate exchange by the forearm skeletal muscle in hyperglycemic and insulin-treated type II diabetic patients. 222 81

The prevalence and clinical features of diagnosed mellitus secondary to chronic pancreatitis (CP) were assessed from northern (Hokkaido) to southern (Okinawa) Japan by means of a questionnaire to elucidate whether WHO-classified malnutrition-related diabetes mellitus (MRDM) exists in Japan. Of a total 17,500 diabetic patients, only two (0.011%)-one fibrocalculous pancreatic diabetes (FCPD) and one protein-deficient pancreatic diabetes (PDPD) - exhibited MRDM characteristics. A total of 649 CP were collected and classified into 268 cases with chronic alcoholic pancreatitis (CAP), 150 cases with chronic calcified pancreatitis (CCP) and 231 cases with other CP. The prevalence of diabetes mellitus was found to be 50.7% in CAP, 72.7% in CCP and 22.8% in other CP. Among all diabetics, 56.6% was noninsulin-dependent (NIDDM) and 26.4% insulin-dependent (IDDM). IDDM was most frequent in CP. Satisfactory and less than satisfactory glycemic control was obtained in approximately three quarters of all subjects. Only one quarter showed poor glycemic control. Insulin treatment was frequent in CAP (52.2%) and CCP (61.7%), but less in other CP (27.5%). The prevalence of diabetic retinopathy was observed in 33.1% of all subjects, nephropathy 21.0% and neuropathy 36.3%, respectively. The prevalence of complications, including macroangiopathy tended to be higher in CAP and CCP (40.3 and 56.9%) than in other CP (31.4%).
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PMID:Prevalence and clinical features of diabetes mellitus secondary to chronic pancreatitis in Japan; a study by questionnaire. 224 5

Visits to general practitioners and outpatient clinics were studied among 228 known diabetics and 223 sex and age matched non-diabetic controls. Of the diabetics, 52 were treated with insulin (32 NIDDM, 20 IDDM), 101 with diet plus oral hypoglycaemic agents, and 66 with diet only. Nine were untreated. Information on visits to general practitioners and outpatient clinics during the 12 months preceding ascertainment was obtained from local and national registers. The association between number of visits, subjective symptoms and type of antidiabetic treatment was analysed. The diabetics had a higher score for subjective symptoms and a higher frequency of objective findings than controls. After controlling for these differences, the diabetics in all antidiabetic treatment groups still had a higher number of visits than non-diabetics. Insulin treated diabetics, IDDM or NIDDM, had twice as many visits to physicians due to outpatient clinic visits than the other treatment groups. The costs of treating elderly diabetics may be reduced if these patients are treated more vigorously by diet and oral hypoglycaemic agents in general practice, thus avoiding time-consuming and costly insulin treatment for some of these patients.
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PMID:Why do elderly diabetics burden the health care system more than non-diabetics? 264 95

The effects of an intravenous infusion of porcine GIP on beta-cell secretion in patients with untreated type 2 diabetes mellitus have been studied. The subjects were studied on two separate days. After a 10 h overnight fast and a further 120 min basal period they were given an intravenous infusion of porcine GIP (2 pmol.kg-1.min-1) or control solution in random order from 120-140 min. Frequent plasma glucose, insulin, C-peptide and GIP measurements were made throughout and the study was continued until 200 min. Plasma glucose levels were similar throughout both tests. During the GIP infusion there was an early significant rise in insulin concentration from 0.058 +/- 0.006 nmol/l to 0.106 +/- 0.007 nmol/l (P less than 0.01) within 6 min of commencing the GIP infusion and insulin levels reached a peak of 0.131 +/- 0.011 nmol/l at 10 min (P less than 0.01). Insulin levels remained significantly elevated during the rest of the GIP infusion (P less than 0.01-0.001) and returned to basal values 20 min post infusion. No change in basal insulin values was seen during the control infusion. C-peptide levels were similarly raised during the GIP infusion and the increase was significant just 4 min after commencing the GIP infusion (P less than 0.05). GIP levels increased from 16 +/- 3 pmol/l prior to the infusion to a peak of 286 +/- 24 pmol/l 20 min later. At 4 min when a significant beta-cell response was observed GIP levels were well within the physiological range.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose dependent insulinotropic polypeptide (GIP) infused intravenously is insulinotropic in the fasting state in type 2 (non-insulin dependent) diabetes mellitus. 264 5

In order to evaluate the choice among alternatives quantitatively, a formal decision model must be developed. Yet the literature does not currently include the information required to develop this model. Data tell us very little about what factors should be considered in the choice of treatment for NIDDM patients. Table 1 summarizes some of the advantages and disadvantages of insulin, sulfonylureas, and dietary treatments. Insulin may have the greatest effect upon blood glucose, but may also be associated with the greatest likelihood of nuisance for the patient. At the other extreme, dietary treatment may be safe, but may have a low probability of achieving long-term blood glucose control. There is remarkably little in the literature that considers nuisance factors for the patient, minor but persistent side effects, or the likelihood of other physical changes such as weight gain. We know even less about how to integrate preferences for benefits and side effects into a comprehensive decision. Although some profiles of laboratory results clearly dictate a treatment protocol, there is considerable variability in the treatment options for a large number of NIDDM patients. Consider, for example, the patient who has a fasting blood glucose of 250 mg/dl but no symptoms. There may be several treatment alternatives. Yet the chances of therapeutic success could be influenced by the patient's concern about being dependent upon medication, willingness to comply with life-style changes, and fear of using needles. We suggest that the patient must be active in negotiating the choice of treatment, and that patient preferences for expected outcomes, side effects, and nuisance factors need to be considered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Trade-offs in treatment alternatives for non-insulin-dependent diabetes mellitus. 265 3

This study was initiated in order to evaluate the clinical efficacy of glipizide treatment in 18 patients with non-insulin dependent diabetes mellitus in poor glycemic control with insulin. Insulin dose was kept constant, and various facets of carbohydrate and lipid metabolism were evaluated before and from 4-6 months after the addition of glipizide. The results indicated that fasting and post-prandial glucose concentration were significantly (P less than 0.001) reduced following glipizide treatment, associated with a commensurate fall in glycosylated hemoglobin concentration. The average fall in fasting plasma glucose concentration in the total patient group approximated 60 mg/dl, and the mean decrement in 8 of the 18 patients who had a fall of more than 70 mg/dl in fasting glucose was 93 mg/dl. These results demonstrate that the addition of glipizide to the treatment program of patients with non-insulin dependent diabetes mellitus poorly controlled on insulin can lead to substantial clinical benefit.
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PMID:The combined use of insulin and sulfonylurea therapy in patients with non-insulin dependent diabetes mellitus. 266 91

The importance of genetic factors in the aetiology of NIDDM has been underlined by study of family pedigrees and identical twin pairs. Although in some isolated populations and a tiny minority of Western families inheritance follows an autosomal dominant pattern, a polygenic mode of transmission predominates in Europe and North America. No genetic markers have been identified despite intensive study of the HLA system and gene polymorphisms. Environmental factors appear to play some role, but examination of the evidence for an aetiological effect of the commonly assumed factors, diet and obesity, suggests that they exert no direct effect. However, it is likely that these factors together with physical inactivity could modulate the speed of progression to symptomatic disease. Both beta cell dysfunction and tissue insulin insensitivity are important in producing the syndrome of NIDDM. Insulin insensitivity is present from very early in the time course of the syndrome, but it is clear that the disease cannot develop in the absence of beta cell dysfunction. The recent discovery of islet associated amyloid is exciting as it represents a major step in tracing the pathogenesis of NIDDM backwards towards genetic and non-genetic aetiological influences.
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PMID:Aetiology of non-insulin dependent diabetes. 267 75


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