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Biomedical subjects

P Raskin

Publications and source records attributed to P Raskin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Nephropathy and hypertension in diabetes.

The treatment of the patient with diabetes, with or without hypertension, is complex and challenging. Hyperglycemic treatment should ideally not only control blood glucose, but also prevent the chronic complications and associated metabolic derangements that can lead to increased morbidity and mortality. Hypertensive treatment should not only decrease blood pressure, but also reduce the risk of macrovascular and microvascular disease. The use of antihypertensive agents that improve insulin resistance, dyslipidemia, glycemic control, and nephropathy is preferred whenever possible. The real key to success in the care of the hypertensive diabetic patient is adequate screening and appropriate, early treatment. Currently, there is ample evidence to support the use of intensive management with the goal of near-normalization of blood glucose levels in most patients with diabetes. Similarly, aggressive treatment of hypertension is the current standard. Accomplishing these goals helps to prevent the development of chronic diabetic complications, including nephropathy. ESRD need not be the inevitable outcome for individuals with early diabetic nephropathy. Interventions currently available that are targeted at the known modifiable risk factors underlying the development and progression of diabetic nephropathy offer the best hope for reducing the incidence and severity of this complication. Prevention of the complications of diabetes, including nephropathy, must be the goal for the future on behalf of all those who now have diabetes.

Albuminuria↗
PubMed1998

Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension.

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses > or = 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

Aged↗
PubMed1998

Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients.

The objective of this study was to determine the safety, efficacy, and tolerability of the alpha-glucosidase inhibitor miglitol vs. the sulfonylurea glyburide in the treatment of elderly patients with type 2 diabetes mellitus, inadequately controlled by diet alone. This was a double-blind, randomized, placebo-controlled, 1-yr trial of miglitol 25 mg TID and 50 mg TID compared with placebo and a titrated dose of glyburide in a parallel group comparison study conducted in 30 out-patient sites across the United States. Four hundred eleven (411) diet-treated patients age 60 yr or greater were randomized to receive either placebo TID (n = 101), miglitol 25 mg TID (n = 104), miglitol 50 mg TID (n = 102), or a once-daily dose of glyburide titrated based on fasting plasma glucose (FPG) (n = 104), for a period of 56 weeks. Efficacy was assessed by glycated hemoglobin (HbA1c), fasting and post-meal glucose, insulin, and lipid levels, and by 24-h urinary excretion of glucose and albumin. Safety and tolerability were assessed by tabulation of adverse events, periodic laboratory determinations, and home blood glucose monitoring. HbA1c treatment effects (placebo-subtracted change in HbA1c from baseline) at the 1-yr endpoint were -0.49%, -0.40%, and -0.92% in the miglitol 25 mg TID, miglitol 50 mg TID, and glyburide groups, respectively (P < 0.05- 0.01 vs. placebo). Postprandial insulin levels were significantly greater than placebo and miglitol in the glyburide group (P < 0.01). Hypoglycemia, weight gain, and both routine and serious cardiovascular events were more frequent in the glyburide group (P < 0.05-0.01 vs. placebo or miglitol groups). Diarrhea (or soft stools) and flatulence were more common in both miglitol groups than in the other two groups in a dose-dependent manner, but resulted in relatively few study dropouts. Treatment with miglitol offers the elderly type 2 diabetic patient significant reductions in daylong glycemia as measured by HbA1c. The greater HbA1c reductions seen with once-a-day glyburide occurred at a cost of significant increases in weight, insulin levels, and the incidences of clinical and subclinical hypoglycemia, which did not occur in the miglitol groups. alpha-glucosidase inhibitors are a useful and relatively safe therapeutic option in the elderly patient with type 2 diabetes.

1-Deoxynojirimycin↗
PubMed1998

Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of tramadol in treating the pain of diabetic neuropathy. BACKGROUND: The pain of diabetic neuropathy is a major cause of morbidity among these patients and treatment, as with other small-fiber neuropathies, is often unsatisfactory. Tramadol is a centrally acting analgesic for use in treating moderate to moderately severe pain. METHODS: This multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group study consisted of a washout/screening phase, during which all analgesics were discontinued, and a 42-day double-blind treatment phase. A total of 131 patients with painful diabetic neuropathy were treated with tramadol (n=65) or placebo (n=66) tramadol, which were administered as identical capsules in divided doses four times daily. The primary efficacy analysis compared the mean pain intensity scores in the tramadol and placebo groups obtained at day 42 of the study or at the time of discontinuation. Secondary efficacy assessments were the pain relief rating scores and a quality of life evaluation based on daily activities and sleep characteristics. RESULTS: Tramadol, at an average dosage of 210 mg/day, was significantly (p < 0.001) more effective than placebo for treating the pain of diabetic neuropathy. Patients in the tramadol group scored significantly better in physical (p=0.02) and social functioning (p=0.04) ratings than patients in the placebo group. No statistically significant treatment effects on sleep were identified. The most frequently occurring adverse events with tramadol were nausea, constipation, headache, and somnolence. CONCLUSIONS: The results of this placebo-controlled trial showed that tramadol was effective and safe in treating the pain of diabetic neuropathy.

Activities of Daily Living↗
PubMed1998

Obesity-independent hyperinsulinemia in nondiabetic first-degree relatives of individuals with type 2 diabetes.

A close association between obesity and hyperinsulinemia is well recognized, but it is not known whether this relationship is affected by the genetic susceptibility to type 2 diabetes. Insulin response to a 75-g oral glucose load was evaluated in healthy nondiabetic Caucasians with first-degree family history of diabetes (relatives, n = 55) and those without family history (nonrelatives, n = 33). A significant correlation between the BMI and insulin response (area under the curve [AUC] during the 2-h period) was seen in nonrelatives (r = 0.68, P < 0.0001) but not in the relatives (r = 0.12, P = 0.37). Multivariate analysis revealed that obesity (BMI) was the primary determinant of insulin response in nonrelatives (P < 0.001), whereas among the relatives, BMI had no significant impact (P = 0.28). Thus, these distinctions between the relatives and nonrelatives remained after adjusting for glucose level, age, and gender. Among first-degree relatives, the commonly observed association between BMI and insulin response is lost, and hyperinsulinemia is present even in the absence of obesity. First-degree family history of diabetes may confer insulin resistance that is independent of obesity. Alternatively, this could suggest a pathological regulation of an obesity-insulin feedback loop, e.g., a defective recognition of adiposity.

Adult↗
PubMed1998

Improved glycemic control in intensively treated type 1 diabetic patients using blood glucose meters with storage capability and computer-assisted analyses.

OBJECTIVE: To determine the effect on glycemic control in intensively treated type 1 diabetic patients using a blood glucose meter with storage capability and computer-assisted analyses. RESEARCH DESIGN AND METHODS: Glycemic control was assessed in 22 intensively treated adults with type 1 diabetes for 12 months while using a meter without memory, followed by 12 months while using a meter with memory. Log books were used to assist patients in managing aspects of the diabetes treatment plan during the first 12-month period, and computer-assisted analyses were used when the meter with memory was used. GHb levels were measured monthly throughout the 24 months of observation. RESULTS: The mean GHb level averaged across all patients during the period of memory meter use (6.4%) was significantly lower than that during the period of meter use without memory (6.9%) (P=0.0004). The change in GHb levels from each period-specific baseline level occurred at significantly different slopes (P=0.046) when adjusted for baseline GHb level. In addition, the downward trend in GHb level was greater in those patients who increased the frequency of testing the most (r=-0.54, P=0.01). CONCLUSIONS: Use of a meter with memory in conjunction with computer-generated analyses of stored blood glucose test results can lead to improved glycemic control when used by a group of intensively treated adult diabetic patients. Improvement in glycemic control was related to frequency of blood glucose testing.

Adult↗
PubMed1997

Glycemic control and cardiopulmonary function in patients with insulin-dependent diabetes mellitus.

BACKGROUND: We studied cardiopulmonary function during exercise in young subjects with long-standing insulin-dependent diabetes mellitus (IDDM) who have no clinical cardiopulmonary disease to determine the relationships of aerobic capacity, gas exchange, ventilatory power requirement, and cardiac output to chronic glycemic control. METHODS: Eighteen subjects with IDDM and 14 normal control subjects were studied. Nine diabetic subjects received twice daily insulin injections and had chronically elevated levels of glycosylated hemoglobin (hyperglycemic group); 9 other diabetic subjects received insulin via continuous infusion pumps and maintained chronic near-normal levels of glycosylated hemoglobin (normoglycemic group). At the end of at least 7 years of regular follow-up, aerobic capacity was determined by cycle ergometry. Lung volume, diffusing capacity, and cardiac output during exercise were measured by a rebreathing technique. Ventilatory power was measured by the esophageal balloon technique. RESULTS: Maximal work load and oxygen uptake were markedly impaired in chronically hyperglycemic diabetic patients associated with significant restrictions of lung volume, lung diffusing capacity, and stroke index during exercise. Membrane diffusing capacity was significantly reduced at a given cardiac index. The normoglycemic patients consistently showed less impairment than the hyperglycemic patients. CONCLUSION: Physiologically significant cardiopulmonary dysfunction develops in asymptomatic patients with long-standing IDDM. Chronic maintenance of near-normoglycemia is associated with improved cardiopulmonary function.

Adult↗
PubMed1997

Essential hypertension is associated with decreased insulin clearance and insulin resistance.

Essential hypertension is associated with multiple metabolic abnormalities, among them, hyperinsulinemia. This hyperinsulinemia is attributed to the presence of decreased insulin sensitivity (insulin resistance) with consequent compensatory insulin secretion. We tested the hypothesis that decreased insulin clearance is present in hypertensive subjects and contributes to hyperinsulinemia independently of the degree of insulin resistance. Seventy-five subjects were studied (48 hypertensive and 27 normotensive). Both groups were comparable in terms of age, body fat content, waist-to-hip ratio, and sex distribution. A primed continuous insulin infusion at 40 mU/m2 per minute was performed. Glucose was maintained at baseline levels with the euglycemic clamp technique. Hypertensive subjects were characterized by decreased insulin sensitivity (insulin-mediated glucose uptake: 5.14 +/- 0.28 versus 7.26 +/- 0.61 mg glucose/kg fat-free mass per minute, hypertensive versus normotensive, P = .002), increased insulin levels during the insulin infusions (804 +/- 36 versus 510 +/- 38 pmol/L, hypertensive versus normotensive, P < .001), and decreased insulin metabolic clearance rate (328 +/- 15 versus 521 +/- 30 mL/min per meter squared, hypertensive versus normotensive, P < .001). In an ANCOVA (including sex, degree of obesity, waist-to-hip ratio, and insulin sensitivity as covariates) the differences in insulin metabolic clearance rate between normotensive and hypertensive subjects remained highly significant (P < .001). Insulin metabolic clearance rate was significantly associated with fasting insulin levels. We conclude that essential hypertension is independently associated with decreased insulin metabolic clearance rate in addition to insulin resistance. A low insulin metabolic clearance rate may be a contributory factor to the hyperinsulinemia observed in essential hypertension.

Analysis of Variance↗
PubMed1997

A double-masked placebo-controlled trial assessing effects of various doses of BTS 67,582, a novel insulinotropic agent, on fasting hyperglycemia in NIDDM patients.

OBJECTIVE: To determine the effect over a 4-week period of varying doses of BTS 67,582, a novel nonsulfonylurea insulinotropic agent, on fasting plasma glucose (FPG) levels in sulfonylurea-responsive NIDDM patients. RESEARCH DESIGN AND METHODS: This was a 12-week multicenter, double-masked, placebo-controlled trial. Patients entered a 4-week stabilization period during which they received their previously prescribed sulfonylurea. Qualified patients (FPG < or = 10 mmol/l) then entered a 4-week sulfonylurea withdrawal single-masked placebo run-in period. Qualified patients (FPG 8.9-16.7 mmol/l) were randomized to either placebo (n = 14), 50 mg b.i.d. BTS 67,582 (n = 18), 250 mg b.i.d. BTS 67,582 (n = 18), 500 mg b.i.d. BTS 67,582 (n = 15), 100 mg q.d. BTS 67,582 (n = 17), or 500 mg q.d. BTS 67,582 (n = 16). The primary efficacy variables were mean changes from baseline in FPG and fructosamine (FRUC). Additional variables included mean changes from baseline in HbA1c, fasting serum insulin (FSI), and fasting serum C-peptide. RESULTS: After 4 weeks of treatment, all BTS 67,582 dose groups showed a decrease from baseline in FPG and FRUC compared with the placebo group. The treatment groups of 250 mg b.i.d. (-3.1 +/- 0.7 mmol/l), 500 mg b.i.d. (-2.3 +/- 0.6 mmol/l), and 500 mg q.d. (-1.2 +/- 0.7 mmol/l) had statistically significant (P < 0.05) decreases in FPG compared with placebo (0.7 +/- 0.6 mmol/l). Similarly, there were statistically significant (P < 0.05) decreases from baseline in FRUC for the 250 mg b.i.d (-55 +/- 10 mumol/l), 500 mg b.i.d. (-40 +/- 12 mumol/l), and 500 mg q.d. (-13 +/- 9 mumol/l) treatment groups compared with placebo (15 +/- 11 mumol/l). Although the treatment period was only 4 weeks in duration, there were also significant differences (P < 0.05) in the HbA1c changes from baseline for the 250 mg b.i.d. (0.0 +/- 0.1%) and 500 mg b.i.d. (-0.2 +/- 0.1%) treatment groups compared with placebo (0.6 +/- 0.2%). There were no significant differences among the treatment groups in the changes from baseline for FSI or C-peptide levels. The most frequently reported side effects were headache, asthenia, infection, and thirst, and the incidence of these events as well as the incidence of study drug discontinuation was comparable in all treatment groups including placebo. CONCLUSIONS: Four weeks of treatment with BTS 67,582 at doses of 250 mg b.i.d. and 500 mg b.i.d. in NIDDM patients was effective in reducing FPG and FRUC, with significant results also seen for HbA1c. The drug was well tolerated with an incidence of discontinuations and laboratory side-effect safety profiles comparable to placebo. BTS 67,582 is a safe and effective oral treatment for NIDDM patients.

Adult↗
PubMed1996

Hypertension in diabetes mellitus.

Hypertension should be detected and treated early in diabetic patients. It has a marked contribution to the morbidity and mortality of diabetic individuals due to both atherosclerosis and microvascular disease. Antihypertensive treatment is an effective tool in slowing the progression of early and advanced diabetic nephropathy. Prospective studies addressing the effects of antihypertensive regimens on the incidence of CHF, stroke, and coronary artery disease in the diabetic population are not available. We assume that the beneficial effects of therapy apply to both diabetic and nondiabetic subjects. Glycemic control and the lipid profile are major concerns when selecting an antihypertensive drug. Because hyperinsulinemia and insulin resistance have been advocated as hypertensive and atherosclerotic risk factors, the effects of antihypertensive drugs on insulin action and plasma insulin levels may also become an important element in the selection of an antihypertensive agent. ACE inhibitors, calcium channel blockers, and alpha-adrenergic blockers probably offer the most favorable metabolic profile when compared with diuretics and beta-blockers and should be used as the initial drugs in most clinical settings.

Antihypertensive Agents↗
PubMed1996

Relationship between insulin sensitivity, hyperinsulinemia, and insulin-mediated sympathetic activation in normotensive and hypertensive subjects.

The adrenergic response to high physiological hyperinsulinemia was studied in 39 hypertensive subjects (28 men and 11 women) and 25 normal volunteers (15 men and 10 women), using the euglycemic clamp technique. Control studies using 0.45% saline infusions (sham studies) were also performed. Before and during the clamp procedure, plasma norepinephrine (NE) and epinephrine (E) were measured using a high performance liquid chromatographic method (HPLC). The association between the increment in NE and E levels and insulin sensitivity, steady-state insulin level during the clamps, waist to hip ratio (WHR), baseline NE levels and gender was studied. NE levels increased during the hyperinsulinemic period (mean increase 46 +/- 6 pmol P < .001 upsilon baseline and P < .01 upsilon sham studies). E levels did not differ between the insulin clamps and the sham studies. Insulin sensitivity was not significantly associated with the increment in NE. Hypertensive subjects had a higher NE increase than the normotensive individuals (55 +/- 7 upsilon 30 +/- 10 pmol, P = .03), but also had higher insulin levels during the clamps (839 +/- 43 upsilon 522 +/- 38 pmol, P < .001). Insulin levels accounted for most of the differences in NE increase between the normotensive and hypertensive groups. Gender, adiposity and WHR were also associated with NE increment. We conclude that the insulin mediated sympathetic activation is not affected in the presence of decreased insulin sensitivity for glucose utilization. The greater degree of sympathetic activation observed in hypertensive subjects is a function of the level of insulinemia obtained during the clamps.

Blood Glucose↗
PubMed1995

Efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia.

PURPOSE: Patients with type I and type II diabetes mellitus have an increased risk of coronary heart disease. In many diabetics, hypercholesterolemia is present and further exacerbates this risk. We investigated the efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia. PATIENTS AND METHODS: In this 24-week, multi-center, double-blind, placebo-controlled study, 94 patients (45 men, 49 women), 18 to 70 years of age, with type I or type II diabetes mellitus and hypercholesterolemia (fasting plasma low-density lipoprotein cholesterol [LDL-C] levels > 150 mg/dL and above the 75th percentile for the US population by age and gender) were randomized to receive pravastatin 20 mg hs or matching placebo. Two patients were randomized to treatment with drug for every 1 randomized to placebo. The dose could be doubled after 10 weeks, and cholestyramine or colestipol could be added after 18 weeks, as needed, to attempt to lower the LDL-C levels to below the 50th percentile for the US population. RESULTS: Significant reductions in LDL-C (-27.6%), total cholesterol (-22.1%), very-low-density lipoprotein cholesterol (-22.6%), and triglycerides (-12.8%) (P < or = 0.001 versus placebo for all reductions), and significant increases in high-density lipoprotein cholesterol (4.4%) (P < or = 0.05 versus placebo) were noted in the pravastatin treatment group (average dose 29.5 mg) at 16 weeks. The beneficial lipid-lowering effects of pravastatin were maintained throughout the 24 weeks of the study. Pravastatin was well tolerated, and the frequency of side effects was similar in the pravastatin and placebo groups. No clinically significant changes in the control of diabetes, as assessed by fasting blood glucose levels and glycosylated hemoglobin measurements, were seen during this study. CONCLUSION: The results of this study demonstrate that pravastatin is well tolerated and effective in lowering total cholesterol and LDL-C in patients with type I or type II diabetes mellitus and hypercholesterolemia.

Adult↗
PubMed1995

Kinetics of glucose delivery to subcutaneous tissue in rats measured with 0.3-mm amperometric microsensors.

The time between intravenous injection of a glucose bolus and the time the glucose concentration peaked in the subcutaneous tissue was measured in pentobarbital-anesthetized rats with implanted 290-microns-diameter amperometric sensors. Boluses of 100, 200, and 400 mg/kg body wt were injected. The glucose concentration in the jugular vein was monitored by frequent withdrawal and analysis of samples. The glucose concentration in the subcutaneous tissue was continuously monitored with the sensors. The times required for the subcutaneously implanted sensor to reach its maximum current, corrected for sensor response times, were 7.5 +/- 3.9, 9.8 +/- 5.5, and 10.0 +/- 4.4 min for the smallest to the largest dose, respectively. The shorter delay in response to the smallest dose was statistically significant (P < 0.03). The results were consistent with dilution of the bolus in the cardiovascular system and transport of glucose by both diffusion and facilitated transport via a saturable mediator. An understanding of the differences in the dynamics of venous vs. subcutaneous response to a glucose dose is important in developing algorithms for the control of blood glucose based on a subcutaneous measurement.

Animals↗
PubMed1995

A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM.

OBJECTIVE: To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Forty subjects (18 men and 22 women; aged 53.9 +/- 7.0 years) with NIDDM and hyperlipidemia were randomly assigned to one of four treatment groups: 9 g of fish oil, 18 g of fish oil, 9 g of corn oil, or 18 g of corn oil daily supplementation for 12 weeks. RESULTS: The level of oil supplements (9 g compared with 18 g) did not have a significant effect within each oil group on glycemic control and lipids. Significant differences (P < 0.05) in lipids were found when the 9-g and 18-g groups were combined. In subjects consuming fish oil, plasma very-low-density lipoprotein (VLDL) cholesterol (P = 0.0001), plasma triglyceride (TG) (P = 0.0001), and plasma VLDL TGs (P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks) were significantly lowered compared with subjects consuming corn oil. Plasma VLDL cholesterol increased across time in the corn oil group (P = 0.04). Plasma low-density lipoprotein (LDL) cholesterol was temporarily increased (P = 0.008) in the fish oil group at 6 weeks, but the effect was no longer present at 12 weeks. No significant differences between fish oil- or corn oil-supplemented diets were found in total plasma cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, glycosylated HbA1c, weight, and blood pressure. CONCLUSIONS: In this study, fish oil supplementation improved plasma VLDL cholesterol, VLDL TGs, and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM. Furthermore, fish oil supplementation had no significant deleterious effect on glycemic control.

Blood Glucose↗
PubMed1994

Insulin withholding for weight control in women with diabetes.

OBJECTIVE: To provide a description of the clinical characteristics that distinguish individuals who withhold insulin for weight control from those who do not. Some individuals with insulin-dependent diabetes mellitus (IDDM) control their weight by withholding insulin and purging excessive calories. This process places patients at risk for developing severe hyperglycemia, diabetic ketoacidosis, and increases the risk of long-term complications of diabetes. RESEARCH DESIGN AND METHODS: Forty-two women with IDDM, ages 16-40, were interviewed and divided into two groups: insulin withholders (IWs) and non-insulin withholders (non-IWs). These groups were compared on physiological, behavioral, psychological, and psychiatric variables. RESULTS: Compared with non-IWs, patients who withheld insulin to control their weight exhibited poorer glycemic control, reported more negative attitudes toward diabetes, were more likely to have pathological scores on the Eating Disorder Inventory 2, and were more likely to report current or past symptoms of anorexia or bulimia nervosa. IWs were also more likely to report lying to physicians about their degree of compliance with their diabetes regimens. CONCLUSIONS: The results of this study indicated that IWs exhibit more symptoms associated with the spectrum of eating disorders than non-IWs. This study showed that insulin withholding for weight control not only exists, but is associated with some maladaptive symptoms and behaviors that need to be addressed by diabetes treatment teams.

Adolescent↗
PubMed1993

Genes for insulin-dependent diabetes mellitus (IDDM) in the major histocompatibility complex (MHC) of African-Americans.

Mapping the MHC-associated susceptibility and resistance factors for insulin-dependent diabetes mellitus (IDDM) has been difficult due to the strong linkage disequilibrium within the HLA-DR-DQ region. Previous analyses have suggested that the study of IDDM-associated haplotypes in different races might be useful for identifying the responsible genes. We have performed complete HLA class II genotyping to study susceptibility and resistance to IDDM in 34 randomly selected African-American IDDM patients and 69 ethnically-matched controls. IDDM patients showed highly significant increases of DRB1*0301, DRB1*0401, DRB1*0405, DQA1*0301, DQA1*0302, DQB1*0201 and DQB1*0302. Analysis of DQA1-DQB1 associations showed that DQA1*03 combined with both DQB1*0201 and DQB1*0302 gave the highest odds ratio, suggesting a synergistic effect due to formation of heterodimers encoded both in cis and in trans. Among the subsets of DR4, only DRB1*0401 and DRB1*0405 were increased in diabetic patients. Interestingly, DQB1*0602 and DQB1*0301, which have previously been thought to encode resistance factors in Caucasians, were not significantly decreased and, after removal of known susceptibility haplotypes, were found to have essentially identical frequencies in patients and controls.

Adolescent↗
PubMed1993

Insulin requirements in lipodystrophic diabetes.

A ten-fold increase in daily insulin requirements during the administration of total parenteral nutrition (TPN) is described in a patient with congenital generalized lipodystrophy, insulin-requiring diabetes mellitus, and acanthosis nigricans during an episode of acute pancreatitis secondary to hypertriglyceridaemia. After a period of 13 days on TPN, insulin requirements increased dramatically to an average of 1428 units per day for a period of 12 days, to achieve a mean blood glucose level of 10.9 mmol l-1. When the patient resumed feeding and the TPN was discontinued, the average daily insulin requirement was 104 units with a mean 24 h blood glucose of 11.8 mmol l-1. Parenteral administration of energy substrates in a rare case of diabetes mellitus and congenital lipodystrophy complicated by acute pancreatitis resulted in a severe insulin insensitive state due to the combination of the hypermetabolism conferred by the pancreatitis plus transient impairments of the glucose disposal mechanism by the energy substrates provided.

Acanthosis Nigricans↗