Non-insulin-dependent Diabetes Mellitus Controls Research Articles

Synthesis and antidiabetic activity of novel triazole derivatives containing amino acids

AbstractNew series of triazole derivatives coupled with amino acids 1a‐h were obtained via multicomponent reaction of 2‐hydroxy benzaldehyde or 2‐hydroxy acetophenone with thiosemicarbazide and different amino acids. The obtained compounds were reacted with p‐toluinesulfonyl chloride 2 to give the corresponding sulfonamides 3a‐h. Compound 1b was allowed to react with different aromatic aldehydes or cyclic ketone under alkaline conditions to afford the expected imino compounds 4a‐d and 6a‐c, respectively. These compounds were allowed to react with ethyl glycolate to yield the expected thiazolidinone derivatives 5a‐d or 7a‐c, respectively. Structures of the newly synthesized compounds were found to be in accordance with their elemental analyses and spectral data. The obtained compounds exhibited very prominent in vitro and in vivo antihyperglycemic effect at a dose of 40 mg/kg body weight compared to the standard drug gliclazide and control. The antidiabetic effect was investigated using oral glucose tolerance test in normal and non‐insulin‐dependent diabetes mellitus (NIDDM) in STZ‐rat model. Compounds 3a‐h, 5b, 5c, 5d, 7a, 7b, and 7c showed significant activity in lowering blood glucose (more than 80%) compared to the NIDDM control.

Effect of Withania somnifera on Insulin Sensitivity in Non‐Insulin‐Dependent Diabetes Mellitus Rats

We investigated the effect of an aqueous extract of Withania somnifera (WS) on insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (100 mg/kg) to 2 days old rat pups. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e. 75 days after streptozotocin injection). A group of citrate control rats (group I) were also maintained that has received citrate buffer on the second day of their birth. A significant increase in blood glucose, glycosylated haemoglobin (HbA(1)c) and serum insulin levels were observed in NIDDM control rats. Treatment with WS reduced the elevated levels of blood glucose, HbA(1)c and insulin in the NIDDM rats. An oral glucose tolerance test was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with WS. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. WS treatment significantly improved insulin sensitivity index (K(ITT)) that was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas WS treatment significantly prevented the rise in HOMA-R in NIDDM-treated rats. Our data suggest that aqueous extract of WS normalizes hyperglycemia in NIDDM rats by improving insulin sensitivity.

Effect of <i>Lycium barbarum</i> Polysaccharide on the Improvement of Insulin Resistance in NIDDM Rats

Lycium barbarum is one of the traditional oriental medicines. It has been reported to reduce blood glucose levels. In this study, the effect of Lycium barbarum polysaccharide (LBP) on the improvement of insulin resistance and lipid profile was studied in rats, a model for non-insulin dependent diabetes mellitus (NIDDM). The rats were divided into three groups: control, NIDDM control, and NIDDM+LBP. Diabetes model groups were made by feeding high-fat diet and subjecting to i.p. streptozotocin (50 mg/kg). LBP treatment for 3 weeks resulted in a significant decrease in the concentration of plasma triglyceride and weight in NIDDM rats. Furthermore, LBP markedly decreased the plasma cholesterol levels and fasting plasma insulin levels, and the postprandial glucose level at 30 min during oral glucose tolerance test and significantly increased the Insulin Sensitive Index in NIDDM rats. In the present study, we have tested that LBP can alleviate insulin resistance and the effect of LBP is associated with increasing cell-surface level of glucose transporter 4 (GLUT4) in skeletal muscle of NIDDM rats. Under insulin stimulus, GLUT4 content in plasma membrane in NIDDM control rats was significantly lower than that of control (p<0.01), and GLUT4 content in the plasma membrane in NIDDM+LBP rats was higher than that of NIDDM control rats (p<0.01). In conclusion, LBP can ameliorate insulin resistance, and the mechanism may be involved in increasing cell-surface level of GLUT4, improving GLUT4 trafficking and intracellular insulin signaling.

The family functioning and glycemic control ofnon-insulin dependent diabetes mellitus

The family functioning and glycemic control ofnon-insulin dependent diabetes mellitus

Are we closer to finding the treatment for type 2 diabetes mellitus in morbid obesity? Are the incretins the key to success?

Morbid obesity is a serious health problem associated with disease and mortality. One such disease is non-insulin-dependent diabetes mellitus (NIDDM). Approximately 95% of American diabetics have NIDDM. One of the major causes for type 2 diabetes is obesity. The improvement of diabetes with weight control is not in the earliest description of the disease. However, dietary control of NIDDM is often disappointing. Diet can improve glucose metabolism in obesity, but the improvement usually represents only a portion or a brief return to euglycemia, even when patients appear to be compliant. In contrast, reversal of NIDDM has been much more successfully achieved after bariatric surgery. Intra-abdominal fat deposition is associated with increased plasma concentration of free fatty acids, which reduce insulin sensitivity at both muscular and hepatic sites. The progression of diabetes is heralded by the inability of the beta-cells to maintain their previously high rate of insulin secretion in response to glucose, in the face of insulin resistance. The propensity to develop type 2 diabetes may be genetically determined or triggered by environmental factors. The connection between diabetes and obesity represents a continuum that progresses through different phases in which defective insulin action is the principal problem. At this point, we are unable to correlate the different findings of the many questions that arise, such as: 1) Does the decrease in sensitivity to insulin result from rearrangement of the insulin receptor? 2) Is weight loss the trigger for decrease of insulin resistance? 3) Is rearrangement of part of the intestine a mechanism to trigger the secretion of hormones (incretins) that help in insulin response? 4) Which mechanism controls the insulin resistance? The goal of this paper is to review literature on incretins and address the role of incretins after bariatric surgery. We know very little about the action of incretins in diabetes. We will assess the interaction between the secretion of incretins and bariatric surgery for the cure of diabetes.

Insulin Subcutaneous Application vs. Continuous Infusion for Postoperative Blood Glucose Control in Patients with Non-Insulin-Dependent Diabetes Mellitus

Background Frequently, the use of insulin is considered for metabolic control in postoperative patients with non-insulin-dependent diabetes mellitus (NIDDM). We sought to determine the best method for control of glucose in NIDDM non-insulin patients during postoperative care. Methods Two algorithms were developed: subcutaneous administration of insulin (SC), and continuous intravenous infusion (IV). A randomized, controlled clinical trial was designed. In addition, both experimental groups were compared with a non-concurrent routinely managed group (RM) with insulin administration under no predetermined algorithm. Eligible patients were those subjected to major surgery under general anesthesia or spinal blockade. They were followed for 48 h after surgery. Target variables were capillary and central blood glucose, insulin dose administered, urine glucose and ketone strip determination, and development of hyper- or hypoglycemia. Results A total of 62 patients were studied (RM = 25, SC = 19, IV = 18). Results for both experimental algorithms were similar except for the IV group that required less insulin per hour compared to SC (0.64 vs. 0.34 U/h; p = 0.0003). The RM control group showed poor control in all capillary glucose measurements (194.9 ± 26.8 mg/dL) compared with the two experimental algorithms (SC = 129.9 ± 21; IV = 131.6 ± 20.4) ( p <0.05). More hyperglycemia events appeared in the RM group ( p = 0.016). Only one hypoglycemia event occurred in the IV group. Conclusions Postoperative control of NIDDM is similar with both tested methods. The use of any of the algorithms studied improves metabolic control substantially because it standardizes postoperative management of the diabetic patient with timely determination of capillary blood glucose and insulin administration. However, IV administration has the advantage of accomplishing adequate control with a smaller insulin dose.

Antihyperglycemic Treatment in Diabetics with Coronary Disease: Increased Metformin-Associated Mortality over a 5-Year Follow-Up

Mortality rates are considerably higher in chronic ischemic heart disease (IHD) patients with non-insulin-dependent diabetes mellitus (NIDDM) than in those who are nondiabetics. The relationship between different types of antihyperglycemic pharmacological therapy and mortality rate in this NIDDM population is uncertain. We aimed to examine the survival in NIDDM patients with IHD using various types of oral antidiabetic treatments over a 5-year follow-up period. The study sample comprised 11,440 patients with a previous myocardial infarction and/or stable anginal syndrome, aged 45–74 years, who were screened, but not included in the Bezafibrate Infarction Prevention study. Among them, 9,045 were nondiabetics and 2,395 diabetics. The diabetic patients were divided into four groups on the basis of their therapeutic regimen at screening: diet alone (n = 990), sulfonylureas (n = 1,041), metformin (n = 78) and a combination of a sulfonylurea and metformin (n = 266). All NIDDM groups were similar with regard to age, gender, hypertension, smoking, heart failure, angina and prior myocardial infarction. Crude mortality rate was lower in the nondiabetic group (11.21 vs. 21.8%; p < 0.001). In the diabetic group, mortality was 18.5% for patients on diet alone, 22.5% for those on sulfonylureas, 25.6% for patients on metformin, and 31.6% for the combined sulfonylurea/metformin group (p < 0.01). When analyzing age-adjusted mortality rate and actuarial survival curves, the lowest mortality was found in patients on diet alone and the highest in patients on metformin (alone or in combination with sulfonylureas). After adjustment for variables connected with long-term prognosis, the use of metformin was associated with increased relative risk (RR) for all-cause mortality of 1.42 (95% CI 1.10–1.85), whereas the use of sulfonylureas alone was not [RR 1.11 (95% CI 0.90–1.36)]. NIDDM patients with IHD using metformin, alone or in combination with sulfonylureas, exhibited a significantly increased mortality. Until the results of problem-oriented prospective studies on oral control of NIDDM will be available, alternative therapeutic approaches should be investigated in these patients.

Double-masked, placebo-controlled, dose-ranging study of troglitazone 10 to 200 mg once daily in non—insulin-dependent diabetes mellitus

Troglitazone is an insulin action-enhancing agent currently being investigated clinically for the treatment of non—insulin-dependent diabetes mellitus (NIDDM). Dose-ranging studies of the metabolic effects of troglitazone in NIDDM patients at doses of up to 800 mg/d have shown effective glycemic control, good tolerability, and favorable effects on dyslipidemic profiles. To determine the minimum effective dose of troglitazone required to achieve glycemic control in NIDDM, 10-mg, 30-mg, 100-mg, and 200-mg doses of troglitazone were administered once daily for 16 weeks in this double-masked, placebo-controlled, parallel-group, dose-ranging study. A total of 284 patients of both sexes (mean age, 60 years; range, 35 to 84 years) with a diagnosis of NIDDM and two consecutive fasting capillary blood glucose levels of 7 to 15 mmol/L, within 4 mmol/L of each other, were randomized to treatment. After 16 weeks of treatment an adjusted geometric mean glycated hemoglobin A 1c (Hb A 1c) value of 7.6% was seen in the 200-mg group compared with 8.2% in the placebo group, resulting in a statistically significant 7% overall reduction in Hb A 1c compared with placebo. Reductions in Hb A 1c in the other treatment groups were not statistically significant when compared with placebo. A definite linear dose-response relationship over the range of 10 to 200 mg of troglitazone for adjusted geometric mean fasting serum glucose level was seen during the 16-week treatment period; doses of 30, 100, and 200 mg showed statistically significant reductions compared with placebo after 16 weeks of treatment. Both adjusted geometric mean fasting serum insulin and proinsulin levels were lower for troglitazone 200 mg compared with placebo at all visits. A 10% reduction in insulin and a 16% reduction in proinsulin compared with placebo were seen at week 16, with only the latter reaching statistical significance. Troglitazone was well tolerated at all doses. The incidence and nature of adverse events were similar for all doses of troglitazone and placebo, with no hypoglycemic events occurring in any study group. This study demonstrated that troglitazone 200 mg once daily may be considered the minimum effective dose for establishing glycemic control in NIDDM

Diabetes mellitus associated with 3243 mitochondrial tRNA Leu(UUR) mutation: Clinical features and coenzyme Q 10 treatment

Diabetes mellitus associated with mitochondrial tRNA mutation at position 3243 (DM-Mt3243) is a new disease. Patients have a distinctly different picture from MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). During observations at the Saiseikai Central Hospital, the following findings were noted in DM-Mt3243 patients: DM-Mt3243 patients are diagnosed earlier with diabetes, compared to NIDDM (non-insulin dependent diabetes mellitus) controls without family history. DM-Mt3243 patients often need insulin more often than NIDDM controls without family history. Post-treatment neuropathy and insulin edema are often found in DM-Mt3243, and the two phenomena possibly have a similar pathophysiology related to mitochondrial dysfunction. Ambiguous psychiatric disorders of functional psychosis are observed frequently in DM-Mt3243. Mild headache is common in DM-Mt3243 cases. Ambiguous neuromuscular abnormaltiies such as sleep disturbance, paresthesia of the legs, edema of the legs, and palpitation may be symptoms associated with mitochondrial dysfunction in DM-Mt3243. Coenzyme Q may be effective in the relief of these neuromuscular symptoms.

Forum Two: Unanswered Research Questions about Metabolic Control in Non-Insulin-dependent Diabetes Mellitus

The participants of Forum Two addressed the unanswered research questions about metabolic control and non-insulin-dependent diabetes mellitus (NIDDM). The most compelling issue was the effect of metabolic control on both the development and progression of macrovascular disease in patients with NIDDM. Associated questions that could be answered by a well-controlled clinical trial related to the goal of blood glucose control in NIDDM in the elderly and in persons with clinical vascular disease. The specific suggestion was a trial similar to the Veterans Affairs Cooperative Study on Glycemic Control and Complications in NIDDM. Another important research issue that was discussed was the benefit of treating other risk factors such as hypertension and hyperlipidemia in diabetic patients. Yet another area discussed was the study of health services delivery to examine the best care-delivery methods for diabetes and other chronic diseases. Other areas of discussion centered on basic research, that is, the fundamental cause of insulin resistance and the genetics of NIDDM and the loss of protection against atherosclerosis in postmenopausal women with diabetes.

Role of yoga in control of hyperglycemia in middle aged patients of non-insulin dependent diabetes mellitus

The effect of 40 days yoga training in 30 hospitalized non-insulin dependent diabetes mellitus (NIDDM) patients has been investigated after stopping the medication. Blood glucose response to oral glucose load measured as area index total (AIT), glycated haemoglobin (GHb) plasma lipids and lipoproteins measurements before and after yoga training have been compared. Yoga training resulted in a significant improvement in AIT, GHb and plasma triglycerides and cholesterol levels. The data suggest that yoga training along with diet and medical management provides an important metabolic control in NIDDM and may have a role in primary prevention of diabetes mellitus.

Insulin response after treatment depends on fasting plasma glucose level in NIDDM

We investigated the relationship between the improvement in insulin secretion and glycemic control in non-insulin-dependent diabetes mellitus (NIDDM). Fifty-two patients were classified into three groups according to their pretreatment fasting plasma glucose (FPG) level: Group A, FPG < 7.8 mM, n = 20; Group B, 7.8 mM ≤ FPG < 11.1 mM, n = 17; and Group C, 11.1 mM ≤ FPG, n = 15. A 75-g oral glucose tolerance test (OGTT) and a glucagon loading test were performed to evaluate insulin secretion before and after treatment. Plasma glucose levels during a 75-g OGTT were decreased significantly after treatment in all groups ( P < 0.01). In Group A, there was no significant change in insulin secretion before and after treatment (1466 ± 213 pM to 1565 ± 191 pM, P = 0.35). In contrast, in Groups B and C, insulin secretion was poor and suppressed initially, but increased significantly when good glycemic control was obtained after treatment (respectively, 587 ± 70 pM to 863 ± 79 pM, P < 0.01, and 621 ± 94 pM to 1236 ± 232 pM, P < 0.01). The degree of improvement in insulin secretion in 75-g OGTT correlated positively with the degree of improvement in FPG level after treatment ( r = 0.5, P < 0.001). However, the C-peptide response to glucagon did not change before and after treatment. In conclusion, impaired insulin secretion recovered by the good glycemic control in NIDDM with FPG levels above 7.8 mM. Therefore, strict glycemic control (FPG below 7.8 mM) seems important for maintaining good insulin secretion.

Different Change in Lipoprotein(a) Levels From Lipid Levels of Other Lipoproteins With Improved Glycemie Control in Patients With NIDDM

To evaluate change both in lipoprotein(a) [Lp(a)] and lipid levels in other lipoproteins in non-insulin-dependent diabetes mellitus (NIDDM) after short-term improvement of glycemic control. We compared Lp(a) levels in 210 NIDDM patients with those in 46 control subjects and evaluated the relationship between glycemic control and Lp(a) levels in diabetic patients. In addition, changes in Lp(a) levels and lipid levels were assessed after the improvement of glycemic control in 54 poorly controlled NIDDM patients. In NIDDM, Lp(a) levels in all patients, 62 patients with HbA1c < 6.0%, and 75 patients with HbA1c between 6.0 and 8.0%, were significantly higher than those in control subjects (19.1 [1.7-106.6], 19.2 [6.0-106.6], and 20.3 [2.7-75.3] vs. 15.4 [2.0-61.7] mg/dl, median [range], P < 0.05). Lp(a) levels in 73 patients with HbA1c of > or = 8.0% (18.7 [1.7-58.8] mg/dl) were not significantly different from those in control subjects. After glycemic control, lipid levels in plasma and in other lipoproteins fell significantly, but Lp(a) did not change (from 18.3 [1.7-58.8] to 18.4 [6.6-95.3] mg/dl). Changes in lipid levels, including Lp(a), did not correlate with those in fasting plasma glucose or HbA1c. These results suggest that elevated Lp(a) levels do not reflect poor glycemic control and that Lp(a) levels are independent of lipid levels in other lipoproteins after improved glycemic control in NIDDM.

Insulin treatment improves relative hypersecretion of amylin to insulin in rats with non-insulin-dependent diabetes mellitus induced by neonatal streptozocin injection

The dissociated release of insulin and amylin in the hyperglycemic state has been reported. This relative hypersecretion of amylin is thought to provide an important insight into how amylin aggregates to form islet amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to characterize the alterations of amylin hypersecretion in NIDDM with exacerbation or amelioration of diabetic control. For this purpose, neonatally streptozocin (nSTZ) diabetic rats were treated with dexamethasone (0.25 mg/kg) or Lente insulin (3 to 5 U/kg) daily for 14 days, and responses of amylin and insulin to 16.7 mmol/L glucose or 10 mmol/L arginine were evaluated in vitro using an isolated perfused pancreas system. nSTZ rats exhibited moderate elevations of plasma glucose compared with normal rats. In the isolated perfused pancreas, the molar ratio of secreted amylin to insulin in response to 16.7 mmol/L glucose by nSTZ pancreas (1.8% ± 0.2%) was significantly greater than that of normal rat pancreas (1.2% ± 0.1%). Plasma glucose levels in nSTZ rats (7.3 ± 0.4 mmol/L) increased with dexamethasone treatment (17.8 ± 1.1 mmol/L, P < .005) and decreased with insulin treatment (5.8 ± 0.4 mmol/L, P < .05). The secreted amylin to insulin ratio in dexamethasone-treated nSTZ rats was significantly greater than that of the controls ( P < .05). Moreover, insulin-treated nSTZ rats exhibited decreased amylin to insulin molar ratios compared with saline-treated nSTZ rats ( P < .05), which had the same levels as normal rats. We concluded that the relative hypersecretion of amylin in NIDDM model rats, which was exacerbated in the state of severe hyperglycemia, could be improved by near-normoglycemia achieved with insulin treatment. These findings imply the possibility that improvement of glycemic control in NIDDM may prevent increased amylin production independently of that of insulin.

Gliclazide. An update of its pharmacological properties and therapeutic efficacy in non-insulin-dependent diabetes mellitus.

Gliclazide is a second generation sulphonylurea oral hypoglycaemic agent used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It improves defective insulin secretion and may reverse insulin resistance observed in patients with NIDDM. These actions are reflected in a reduction in blood glucose levels which is maintained during both short and long term administration, and is comparable with that achieved by other sulphonylurea agents. Gradually accumulating evidence suggests that gliclazide may be useful in patients with diabetic retinopathy, due to its haemobiological actions, and that addition of gliclazide to insulin therapy enables insulin dosage to be reduced. Thus, gliclazide is an effective agent for the treatment of the metabolic defects associated with NIDDM and may have the added advantage of potentially slowing the progression of diabetic retinopathy. These actions, together with its good general tolerability and low incidence of hypoglycaemia have allowed gliclazide to be well placed within the array of oral hypoglycaemic agents available for the control of NIDDM.

Gliclazide: Metabolic and vascular effects—A perspective

Gliclazide is a second-generation sulfonylurea that is widely used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It has been recommended for use on the basis of both its metabolic and nonmetabolic effects. It has a clear beneficial effect on metabolic control in NIDDM. Blood glucose and lipid levels are lowered. The glucose-lowering effects are secondary to both enhanced insulin secretion and a decrease in insulin resistance. The former is due to closure of a K + adenosine triphosphate (ATP) channel in the β cell. The mechanism whereby insulin action on the liver and muscle are potentiated remains unknown. It does not appear to involve the insulin receptor, and although glycogen synthase activation is enhanced, this is probably not specific. It has proven difficult to separate the metabolic effects of gliclazide from the effects of improved control. The metabolic actions are probably also shared with other sulfonylureas. Gliclazide also has beneficial effects on platelet behavior and function and on the endothelium, in addition to improving free radical status. These effects should be beneficial for the prevention of diabetic microangiopathy and macroangiopathy. Some evidence has appeared for the prevention of deterioration of diabetic ret-inopathy, but results are variable and more convincing studies are required. Many of the nonmetabolic effects of gliclazide appear to be unique to this agent. Gliclazide thus appears to be a reasonable choice in the treatment of NIDDM with diet failure, both from the metabolic and nonmetabolic standpoint.

Effect of Conventional and Intensified Insulin Therapy on Free-Insulin Profiles and Glycemic Control in NIDDM

To investigate the effects on 24-h insulin and glucose profiles of two- and four-dose insulin regimens in patients with non-insulin-dependent diabetes mellitus (NIDDM) who have failed oral agent therapy. Ten patients with NIDDM and 10 matched nondiabetic control subjects took part in the study, a randomized crossover trial with 8-wk treatment periods. We determined 24-h profiles of blood glucose and free insulin in control subjects and patients when they were taking oral agents and at the end of each treatment period. The two-dose regimen was mixed (15% regular, 85% NPH) insulin given before breakfast and dinner, and the four-dose regimen was regular insulin given before meals and NPH given at 2200. Patients taking oral agents had higher mean blood glucose than control subjects (mean +/- SE 12.6 +/- 0.6 vs. 4.5 +/- 0.1 mM, P less than 0.0001) and similar 24-h insulin concentrations but lower postprandial insulin concentrations (at breakfast, 87.6 +/- 13.8 vs. 228.6 +/- 29.4 pM, P less than 0.01). Mean 24-h insulin concentrations were the same on two- and four-dose regimens, and both regimens caused basal hyperinsulinemia. Glycemic control also improved. Postprandial insulin peaks were higher at lunch and dinner on the four-dose regimen, and postprandial blood glucose was lower. Fasting proinsulin was elevated in patients compared with the control subjects (25.1 +/- 4.7 pM vs. 5.0 +/- 0.9 pM, P less than 0.001) and was suppressed to normal during insulin treatment. Two- and four-dose insulin regimens can achieve similar glycemic control. Both regimens cause basal hyperinsulinemia but normalize the hyperproinsulinemia observed during failure of oral agent therapy. Four-dose insulin regimens offer few advantages to the glycemic control achieved with two-dose regimens but may be more physiological.

Theoretical and Baseline Considerations for Diet and Weight Control of Diabetes Among Blacks

This article outlines theoretical considerations for diet and weight control of non-insulin-dependent diabetes mellitus (NIDDM) and identifies factors that may be of particular importance in influencing the success of diet and weight control of NIDDM in the Black population. Long-term adherence to dietary or weight-control regimens requires that the patient evaluate and restructure established eating and physical activity patterns. With the use of the social action theory as a conceptual framework, this complex behavioral change task can be understood as a function of the interplay of various self-regulatory mechanisms. These mechanisms are influenced by the person's capabilities for making changes, his/her physical condition and general health status, the physical and social environmental context, and the person's material and social resources. Many of these factors may differ for Blacks and Whites in a direction that suggests a lesser potential for effective diet and weight-loss therapy among Black NIDDM patients. For example, compared with Whites, Blacks are more likely to have limited incomes, low educational attainment, ambivalence about weight control, multiple health problems, and high-fat high-sodium low-fiber diets or food preferences. However, some evidence suggests that state-of-the-art counseling approaches can be as effective for Blacks as for Whites. The challenge is to adapt the types of approaches suggested by the social action theory for culturally appropriate and cost-effective delivery in Black community health-care settings.

Effects of Drugs on Glucose Tolerance in Non-Insulin-Dependent Diabetics (Part II)1

Non-insulin-dependent diabetes mellitus (NIDDM) is being increasingly diagnosed as its importance as a risk factor for the development of cardiovascular disease continues to be recognised. Good metabolic control remains a major goal of drug therapy as it decreases the severity and incidence of diabetic complications. Many drugs have been known to interfere with glucose control, either in a beneficial or, more commonly, in a deleterious fashion. Unfortunately in many instances drug-induced effects have not been looked at specifically in NIDDM. Thiazide diuretics have been shown to cause a deterioration in glucose control not only in the general population but especially in patients who have impaired glucose tolerance. While the effect appears less with potassium supplementation and the lower dosage employed nowadays, thiazide diuretics are best avoided in diabetic patients. Loop diuretics have been reported to reduce glucose control to a lesser extent than thiazides. Although indapamide would appear not to interfere with blood sugar control in NIDDM, higher doses that cause potassium loss may cause a deterioration. β-Adrenoceptor antagonists have been reported to cause a rise in blood sugar and glycosylated haemoglobin in NIDDM. The effect may be more marked in patients on oral hypoglycaemic agents as opposed to diet alone and in those on concomitant thiazide diuretics. The greatest effect was seen with propranolol, and the least with cardioselective and the less lipophilic β-blockers. It is of interest that α-blockade with prazosin seems to antagonise β-adrenoceptor blocker-induced deterioration in glucose control. The calcium antagonists have differing effects which may be structure related. In some, but not all, studies use of the dihydropyridines such as nifedipine has been associated with a deterioration in glucose control in NIDDM. Long term studies are needed to assess definitively their effect on glucose control. Verapamil, on the other hand, has in 1 small study been found to have a beneficial effect on glucose control in NIDDM. Centrally acting α-agonists such as the antihypertensive drug clonidine have not been shown to result in a deterioration in glucose control when used in NIDDM, although there are isolated case reports. Long term therapy with the more specific agonist guanfacine was reported in 1 uncontrolled study to have a beneficial effect on glucose tolerance in NIDDM. Uncontrolled studies suggest that phenothiazines may aggravate diabetic control. The significance of a number of recent observations is not fully clear. The balance of endogenous opioid influences over pancreatic β-cell function in NIDDM patients favours the inhibitory effects of met-enkephalin, and the opiate antagonist naloxone partially restores the acute insulin response to glucose. Aspirin appears to have a dual effect in NIDDM — decreased insulin clearance and tissue sensitivity — with no resultant overall change in glucose levels. There are also a number of drugs that may improve glucose tolerance in NIDDM. A number of studies have reported a fall in glycosylated haemoglobin and 2-hour plasma glucose during treatment with the angiotensin converting enzyme (ACE) inhibitors captopril (post glucose load) and enalapril (postprandial), although the effect is relatively small and nonsignificant in some studies. There are also reports of a reduction in fasting plasma glucose and insulin levels during treatment with the lipid-lowering fibric acid derivatives (clofibrate, bezafibrate and fenofibrate) and possibly nicotinic acid derivatives, suggesting increased tissue sensitivity to insulin. The effect was not seen with gemfibrozil and other lipid-lowering agents. Mebendazole, through insulin secretion, and chloroquine, through reduced hepatic degradation of insulin, have been shown in 2 small studies to improve glucose tolerance in NIDDM. While induction of hepatic drug metabolising enzyme activity has been advanced as a means of improving glucose control, possibly through enhanced peripheral glucose utilisation, studies to date in NIDDM have produced contradictory results. A number of uncontrolled studies suggest that both monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants may improve glucose tolerance. Close monitoring of glucose and glycosylated haemoglobin is recommended where the abovementioned drugs are used in NIDDM. There is evidence that possible effects of new drugs in NIDDM are being recognised increasingly as a requirement in new drug development, particularly with cardiovascular agents.

Effects of Drugs on Glucose Tolerance in Non-Insulin-Dependent Diabetics (Part I)1

Non-insulin-dependent diabetes mellitus (NIDDM) is being increasingly diagnosed as its importance as a risk factor for the development of cardiovascular disease continues to be recognised. Good metabolic control remains a major goal of drug therapy as it decreases the severity and incidence of diabetic complications. Many drugs have been known to interfere with glucose control, either in a beneficial or, more commonly, in a deleterious fashion. Unfortunately in many instances drug-induced effects have not been looked at specifically in NIDDM. Thiazide diuretics have been shown to cause a deterioration in glucose control not only in the general population but especially in patients who have impaired glucose tolerance. While the effect appears less with potassium supplementation and the lower dosage employed nowadays, thiazide diuretics are best avoided in diabetic patients. Loop diuretics have been reported to reduce glucose control to a lesser extent than thiazides. Although indapamide would appear not to interfere with blood sugar control in NIDDM, higher doses that cause potassium loss may cause a deterioration. beta-Adrenoceptor antagonists have been reported to cause a rise in blood sugar and glycosylated haemoglobin in NIDDM. The effect may be more marked in patients on oral hypoglycaemic agents as opposed to diet alone and in those on concomitant thiazide diuretics. The greatest effect was seen with propranolol, and the least with cardioselective and the less lipophilic beta-blockers. It is of interest that alpha-blockade with prazosin seems to antagonise beta-adrenoceptor blocker-induced deterioration in glucose control. The calcium antagonists have differing effects which may be structure related. In some, but not all, studies use of the dihydropyridines such as nifedipine has been associated with a deterioration in glucose control in NIDDM. Long term studies are needed to assess definitively their effect on glucose control. Verapamil, on the other hand, has in 1 small study been found to have a beneficial effect on glucose control in NIDDM. Centrally acting alpha-agonists such as the antihypertensive drug clonidine have not been shown to result in a deterioration in glucose control when used in NIDDM, although there are isolated case reports. Long term therapy with the more specific agonist guanfacine was reported in 1 uncontrolled study to have a beneficial effect on glucose tolerance in NIDDM. Uncontrolled studies suggest that phenothiazines may aggravate diabetic control. The significance of a number of recent observations is not fully clear.(ABSTRACT TRUNCATED AT 400 WORDS)