Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low-dose bedtime insulin therapy in combination with oral hypoglycemic agents (OHAs) has become an alternative treatment for NIDDM subjects with secondary failure to OHA. To assess its clinical efficacy, patient compliance, and its possible side effects, 33 patients with secondary OHA failure were recruited in this study. All of the subjects had experienced poor glycemic control for at least six months on their maximal OHAs before the institution of the bedtime insulin injection. Monotard HM (human insulin zinc suspension) was given at an initial dose of 0.15-0.2 U/kg body weight and was adjusted thereafter. As a whole, low-dose bedtime insulin with OHAs improved glycemic control. According to the clinical response, 10 patients (30.3%) were graded as responders, 12 (36.4%) were partial responders, 10 (30.3%) were non-responders, and one (3%) discontinued insulin therapy. There was no difference in demographic features among these three groups of patients. During this period, eight (25%) cases experienced mild hypoglycemic symptoms. In conclusion, combination of OHAs with a low-dose bedtime insulin injection is an alternative therapy for NIDDM patients with OHA failure.
 ...
PMID:Bedtime intermediate-acting insulin in the treatment of secondary failure to oral hypoglycemic agents. 136 16

The Zn/Cu ratio was examined in the serum of three groups of persons: healthy volunteers, diabetic patients on diabetic diet (NIDDM), and diabetic patients on diabetic diet and insulin (IDDM). Zinc, copper, the Zn/Cu serum ratio, and the blood glucose level were determined during fasting and 2 h after breakfast. Zn and Cu serum levels in NIDDM and IDDM patients were decreased. The Zn/Cu ratio was higher in both groups of diabetic patients. These changes in the Zn and Cu levels as well as in the Zn/Cu ratio were not related to chronic diabetic complications.
 ...
PMID:Zinc and copper in the serum of diabetic patients. 137 73

Zinc status was assessed in 53 diabetic patients: 18 insulin-dependent diabetic patients (IDDM), 22 noninsulin-dependent diabetic patients (NIDDM) treated with oral antidiabetic agents, and 13 insulin-treated, noninsulin-dependent diabetic patients (IRDM). Plasma zinc concentrations were in the usual range for healthy subjects in these three groups (15.3 +/- 0.9 mumol/L). Urinary zinc excretions were elevated in the IDDM group (18.3 +/- 4.1 mumol/24 h; p less than 0.01 vs normal) and in the NIDDM group (17.5 +/- 3.5 mumol/24 h; p less than 0.01 vs normal), but normal in the IRDM group (11.3 +/- 2.4 mumol/24 h). In 14 NIDDM patients treated with transient continuous sc insulin injections, urinary zinc decreased from 16.5 +/- 2.2 mumol/24 h before insulin treatment to 11.5 +/- 0.3 mumol/24 h after insulin treatment without any modification in plasma zinc concentrations.
 ...
PMID:Effects of diabetes type and treatment on zinc status in diabetes mellitus. 137 71

Ion channels in beta cells regulate electrical and secretory activity in response to metabolic, pharmacologic, or neural signals by controlling the permeability to K+ and Ca2+. The ATP-sensitive K+ channels act as a switch that responds to fuel secretagogues or sulfonylureas to initiate depolarization. This depolarization opens voltage-dependent calcium channels (VDCC) to increase the amplitude of free cytosolic Ca2+ levels ([Ca2+]i), which triggers exocytosis. Acetyl choline and vasopressin (VP) both potentiate the acute effects of glucose on insulin secretion by generating inositol 1,4,5-trisphosphate to release intracellular Ca2+; VP also potentiates sustained insulin secretion by effects on depolarization. In contrast, inhibitors of insulin secretion decrease [Ca2+]i by either hyperpolarizing the beta cell or by receptor-mediated, G-protein-coupled effects to decrease VDCC activity. Repolarization is initiated by voltage- and Ca(2+)-activated K+ channels. A human insulinoma voltage-dependent K+ channel cDNA was recently cloned and two types of alpha 1 subunits of the VDCC have been identified in insulin-secreting cell lines. Determining how ion channels regulate insulin secretion in normal and diabetic beta cells should provide pathophysiologic insight into the beta cell signal transduction defect characteristic of non-insulin dependent diabetes (NIDDM).
 ...
PMID:The role of ion channels in insulin secretion. 138 42

The efficiency of clearance of plasma triacylglycerols (TAG) after fatty meals in non-diabetic Caucasian subjects is believed to determine the plasma level of high-density-lipoproteins-cholesterol (HDL-C). It is unknown if this observation holds in diabetic subjects and in other racial groups. In assessing the factors that determine TAG responses to acute fat loading in a tropical African population with a low prevalence of atherosclerotic disease, twenty (nine obese) non-insulin-dependent diabetic (NIDDM) patients with optimal glycaemic control and twelve (six obese) age-matched non-diabetic subjects were given meals containing 50 g fat (in butter) and 75 g carbohydrate (in white bread) over 15 min in the morning after a 12 h overnight fast. The fasting plasma levels of glucose, TAG, total cholesterol (total-C), HDL-C, low-density-lipoprotein-cholesterol, insulin and glycosylated haemoglobin (HBAlc) were estimated; glucose and TAG levels were also measured postprandially for 8 h at 2 h intervals. Postprandial lipaemia was consistently higher in the diabetic patients (about 50-100% more than values obtained in the non-diabetic subjects, even when corrected for differences in body mass) and correlated positively with age and postprandial glycaemia. This defect in TAG clearance was even worse (by about 50%) when glucose tolerance became further impaired after ten of the diabetic patients stopped oral hypoglycaemic treatment for 1 week and the fat-tolerance test was repeated. In the obese non-diabetic subjects, but not those of normal weight, there were significant negative relationships between the postprandial lipaemia and fasting plasma levels of HDL-C and HDL-C: total-C ratio, as reported in Caucasians. It is concluded that age and the ambient glucose concentration appear to be the important determinants of the efficiency of TAG clearance in diabetic subjects. This accords with clinical observations of increased atherogenic liability with increasing age and poorer glycaemic control. The determinants in non-diabetic subjects were less defined, indicating that postprandial lipaemia might be influenced by various factors (obesity as shown here) in different subsets of individuals.
 ...
PMID:Some determinants of postprandial lipaemia in Nigerian diabetic and non-diabetic subjects. 139 Jun

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.
 ...
PMID:Diabetes mellitus and macrovascular complications. An epidemiological perspective. 139 12

Not all patients with diabetes develop clinically significant nephropathy and, for this reason, attention has begun to focus on the risk factors for development of this serious complication. These risk factors have not been quantified to the same degree as those factors associated with more common progressive vascular diseases, such as atherosclerosis. However, studies of pathogenesis and clinical and epidemiological surveys of diabetic nephropathy point to numerous risk categories. Glycemic control, genetic and familial predispositions, renal and glomerular enlargement, glomerular hyperfiltration, and capillary and systemic hypertension can be invoked as contributors to this disease process. This review focuses on hemodynamic alterations and their role in the development and progression of diabetic nephropathy. Increases in GFR, largely driven by increases in plasma flow and capillary pressure, appear in early IDDM and NIDDM. This abnormality of renal vascular control probably is derived from alterations in several vasoactive control systems. In addition, the elevations in capillary pressure may be damaging to the glomerular capillaries. Arterial hypertension is not necessarily present before clinical nephropathy appears; however, it is a usual concomitant of progressive diabetic renal disease. The strongest evidences for the roles of altered systemic and renal hemodynamics in the progression of diabetic renal disease are clinical and experimental studies demonstrating attenuation of the disease process by lowering systemic and capillary pressures with antihypertensive agents, and dietary and glycemic modifications. Thus, although multiple factors probably interact to determine risk for the development of diabetic nephropathy, hemodynamic forces are a particularly important contributor and are especially amenable to therapeutic intervention.
 ...
PMID:Diabetic nephropathy. Metabolic versus hemodynamic considerations. 139 17

NIDDM patients have a two- to fourfold increased risk of CHD relative to nondiabetic subjects. This excess risk is explained only partially by increased levels of standard risk factors. We compared the plasma concentrations of Lp(a) in NIDDM patients (n = 260) and nondiabetic subjects (n = 336) who participated in a population-based study (San Antonio Heart Study). Lp(a) was measured using a monoclonal anti-Lp(a) antibody. NIDDM patients and nondiabetic subjects had similar Lp(a) concentrations for both men (13.6 +/- 1.5 vs. 16.1 +/- 1.4 mg/dl) and women (12.6 +/- 0.8 vs. 15.9 +/- 1.3 mg/dl) (P = 0.361). Duration of diabetes and level of fasting glycemia were not significantly related to Lp(a) concentrations. Lp(a) levels were significantly higher in patients who had higher total and LDL cholesterol levels. We conclude that in a large population-based study, Lp(a) levels are not increased in NIDDM patients.
 ...
PMID:Lp(a) concentrations in NIDDM. 139 99

Previous studies indicate that diets rich in digestible carbohydrates improve glucose tolerance in nondiabetic individuals, but may worsen glycemic control in NIDDM patients with moderately severe hyperglycemia. The effects of such high-carbohydrate diets on glucose metabolism in patients with mild NIDDM have not been studied adequately. This study compares responses to an isocaloric high-carbohydrate diet (60% of total energy from carbohydrates) and a low-carbohydrate diet (35% of total energy from carbohydrates) in 8 men with mild NIDDM. Both diets were low in saturated fatty acids, whereas the low-carbohydrate diet was rich in monounsaturated fatty acids. The two diets were matched for dietary fiber content (25 g/day). All patients were randomly assigned to receive first one and then the other diet, each for a period of 21 days, in a metabolic ward. Compared with the low-carbohydrate diet, the high-carbohydrate diet caused a 27.5% increase in plasma triglycerides and a similar increase in VLDL-cholesterol levels; it also reduced levels of HDL cholesterol by 11%. Plasma glucose and insulin responses to identical standard breakfast meals were studied on days 4 and 21 of each period, and these did not differ significantly between the two diets. At the end of each period, a euglycemic hyperinsulinemic glucose clamp study with simultaneous infusion of [3-3H]glucose revealed no significant changes in hepatic insulin sensitivity; and peripheral insulin-mediated glucose disposal remained unchanged (14.7 +/- 1.4 vs. 16.5 +/- 2.3 microM.kg-1.min-1 on the high-carbohydrate and low-carbohydrate diets, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison of effects of high and low carbohydrate diets on plasma lipoproteins and insulin sensitivity in patients with mild NIDDM. 139 1

Glucokinase, the major enzyme that phosphorylates glucose upon entry into liver and islet beta-cells, has been considered a prime candidate for inherited defects predisposing to NIDDM. Now that the human gene has been isolated, this question has been addressed directly. Polymorphic markers flanking the gene were identified. These markers (microsatellites) are composed of variable numbers of dinucleotide repeats that vary in size, resulting in different alleles. Variably sized alleles can be typed rapidly from genomic DNA of individuals by the PCR. Studies of inheritance of glucokinase genes have revealed significant linkage in families with early-onset NIDDM, or MODY, and mutations have been identified within the coding region of the gene in some families. These studies are extremely encouraging, as they indicate that genes can be identified even in this heterogeneous genetic disorder. This study considers the phenotypes that result from glucokinase defects and the relationship of MODY to NIDDM, and it estimates the role of glucokinase defects in NIDDM in general.
 ...
PMID:Glucokinase and NIDDM. A candidate gene that paid off. 139 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>