Biomedical subjects
Publications and source records attributed to G E Umpierrez.
Type 2 diabetes is the most prevalent form of diabetes, accounting for approximately 90% of cases. This article examines the current classification, diagnostic criteria for diabetes, and screening recommendations and provides a therapeutic strategy for improving glycemic control in patients with type 2 diabetes.
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PURPOSE: Diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) are two medical emergencies characterized by elevated total ketone body concentration. We aimed to determine differences in pathogenesis of ketoacidosis and its metabolic consequences by comparing both at presentation and during treatment, the different metabolic products and hormones involved in the ketoacidotic state. MATERIALS AND METHODS: We studied 12 patients with DKA and 8 patients with AKA. On admission and every 4 hours for 24 hours during treatment, samples were drawn for determination of serum ketone bodies, lactate and pyruvate, insulin, and counterregulatory hormones (glucagon, cortisol, growth hormone, and catecholamines). RESULTS: At presentation, with a similar beta-hydroxybutyrate concentration, patients with DKA had a higher plasma glucose (32 mmol/L vs. 6.6 mmol/L), lower beta-hydroxybutyrate/acetoacetate ratio (3:1 vs. 7:1), and a lower lactate/pyruvate ratio (11:1 vs. 19:1) than patients with AKA (all, P < .01). The mean time to resolve ketoacidosis in patients with AKA (6 +/- 1 hour) was significantly shorter than in patients with DKA (16 +/- 2 hours). At presentation, the mean insulin concentration in patients with DKA and AKA were similarly decreased (7.8 +/- 2 and 10.3 +/- 3 microU/mL, P = not significant [NS]). The mean glucagon level before therapy was 203 +/- 15 pg/mL and 188 +/- pg/mL for patients with DKA and AKA, respectively (P = NS). Levels of cortisol, growth hormone, and epinephrine at presentation and during the first 8 hours of treatment were higher in patients with DKA; however, the difference in these values did not reach statistical significance. During therapy, levels of counterregulatory hormones declined at similar rates and returned to normal values after resolution of ketoacidosis. CONCLUSIONS: Our results indicate that, in addition to a history of diabetes or alcoholism, patients with DKA and AKA differ in their metabolic parameters more than in their hormonal profile. The metabolic profile of DKA is characterized by a higher plasma glucose concentration, and lower beta-hydroxybutyrate to acetoacetate and lactate to pyruvate ratios compared with patients with AKA. The initial hormonal profile in both ketoacidotic states is characterized by similarly decreased insulin levels and elevated levels of counterregulatory hormones.
OBJECTIVE: When presenting with diabetic ketoacidosis (DKA), lean and obese patients differ in their subsequent clinical course. Although lean patients tend to remain insulin dependent, most obese patients recover endogenous insulin secretion and discontinue insulin therapy. The aim of this study was to determine whether obese African-American patients with DKA could be determined to have type 1 or type 2 diabetes based on insulin secretion or the presence of immunological and genetic markers. RESEARCH DESIGN AND METHODS: This was a prospective study that analyzed the clinical characteristics, insulin secretion indices, immunological markers (islet cell, GAD, ICA512, and insulin autoantibodies), and HLA susceptibility genes (DR/DQ) in 131 patients with DKA (77 obese and 54 lean), 51 obese patients with hyperglycemia but no DKA, and 25 nondiabetic subjects. All subjects were African-American. Beta-cell function was evaluated by the C-peptide response to glucagon (1 mg i.v.) within 48 h of resolution of DKA or hyperglycemia. RESULTS: The acute C-peptide response was lower in obese DKA patients (1.0+/-0.1 ng/ml) than in obese patients with hyperglycemia (1.7+/-0.2 ng/ml, P < 0.01), but was higher than that in lean DKA patients (0.2+/-0.1 ng/ml, both P < 0.01). The overall prevalence of autoantibodies in obese subjects with DKA (17%) and obese subjects with hyperglycemia (16%) was lower than that in lean subjects with DKA (65%, P < 0.01). Obese patients with hyperglycemia and positive autoantibodies had lower rates of insulin secretion than those without antibodies. Regardless of body weight, all DKA patients with GAD autoantibodies carried the DQB1*0201 allele. However, there were no significant differences in HLA distribution between the three patient groups. CONCLUSIONS: Our results indicate that most obese African-American patients with DKA have type 2 diabetes characterized by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA genetic association. In contrast, most lean African-American patients with DKA have metabolic and immunological features of type 1 diabetes. At presentation, assessment of beta-cell function and determination of autoimmune markers allow for correct classification of diabetes in African-Americans with hyperglycemic crises.
BACKGROUND: The hospital admission and mortality rates of patients with diabetic emergencies, such as diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar nonketotic syndrome (HHNS), are higher in black patients than in white patients with diabetes. However, there is limited data describing the precipitating events and response to treatment in black patients. Analysis of their clinical characteristics and response to medical therapy is needed to evaluate the impact of programs designed to reduce the development of these acute metabolic complications. METHODS: A prospective evaluation was conducted of 144 consecutive patients with DKA and 23 patients with HHNS admitted to a large inner-city hospital between July 1993 and October 1994. RESULTS: In patients previously diagnosed as having diabetes, poor compliance with insulin therapy was the major precipitating cause for DKA (49%) and HHNS (42%). Alcohol or cocaine abuse was a contributing factor for noncompliance and was present in 35% and 13% of patients with DKA and in 44% and 9% of patients with HHNS, respectively. Newly diagnosed diabetes accounted for 17% of patients with DKA and HHNS. Obesity (body mass index > 28 kg/m2 [the weight in kilograms divided by the square of the height in meters]) was present in 29% of patients with DKA and in 17% with HHNS and was most common in patients with DKA who were newly diagnosed as having diabetes (56%). Patients were treated by residents, who used a low-dose insulin protocol with an algorithm for insulin adjustment in 88 of 144 patients with DKA and 14 of 23 patients with HHNS. Although there was no difference in mortality rates or time needed to correct hyperglycemia or ketoacidosis, the use of the protocol significantly reduced the risk of hypoglycemia (5%) compared with patients treated without a protocol (23%) (P < .01). CONCLUSIONS: In urban black patients, poor compliance with insulin therapy was the main precipitating cause of acute metabolic decompensation, and substance abuse was a significant contributing factor for noncompliance. Obesity is common in black patients with DKA; it was present in more than half of those with newly diagnosed diabetes. Improved patient education and better access to medical care might reduce the development of these hyperglycemic emergencies.
A case of bilateral adrenal myelolipoma in association with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency is presented. The clinical, radiologic, and endocrinologic features of this case are correlated with a review of the literature.
OBJECTIVE: Many newly diagnosed obese African-American patients with history of severe hyperglycemia or diabetic ketoacidosis (DKA) are able to discontinue pharmacological treatment with continued good metabolic control. However, many of these individuals relapse into hyperglycemia within 1 year. In such patients, we compared the effect of low-dose sulfonylurea and dietary therapy in the prevention of recurrence of hyperglycemia. RESEARCH DESIGN AND METHODS: We conducted an intention-to-treat study in 35 obese newly diagnosed diabetic patients (17 with DKA and 18 with severe hyperglycemia). After discontinuation of insulin, seven of 17 patients with DKA and seven of 18 patients with hyperglycemia were managed with diet and glyburide (1.25-2.5 mg/day), whereas other patients were followed with diet alone. In all patients, pancreatic insulin reserve was documented 1 day after resolution of hyperglycemic crises and within 1 week of discontinuation of insulin. Recurrence of hyperglycemia was defined as fasting blood glucose > 7.8 mmol/l (140 mg/dl) or random blood glucose > 10 mmol/l (180 mg/dl) on two or more consecutive determinations, or HbA1c > 7.5%. RESULTS: Both treatment groups were comparable in age, sex, duration of diabetes, months of insulin therapy, BMI, glucose, and HbA1c. At presentation, the acute C-peptide response to glucagon in obese DKA patients was lower than in patients with hyperglycemia (P < 0.01), but responses were comparable after discontinuation of insulin. Sulfonylurea treatment significantly reduced recurrence of hyperglycemia in both obese DKA and obese hyperglycemic patients (P = 0.03). With a median follow-up of 16 months, hyperglycemia recurred in six of 10 DKA patients and in five of 11 hyperglycemia patients treated with diet alone, compared with one of seven DKA and one of seven hyperglycemia patients treated with glyburide. Readmission with metabolic decompensation occurred in four patients treated with diet but in none of the patients treated with diet and glyburide. CONCLUSIONS: Low-dose sulfonylurea therapy prevents recurrence of hyperglycemia in newly diagnosed obese African-American patients with a history of hyperglycemic crises.
PURPOSE: To describe the clinical, histologic, and radiologic findings in patients with diabetic muscular infarction (DMI). MATERIALS AND METHODS: Descriptive case series of 3 patients with DMI and 22 previously reported cases (MEDLINE data base search) in the English literature are presented. RESULTS: Diabetic muscular infarction is usually seen in patients with long-standing insulin-dependent diabetes and multiple end-organ microvascular complications. Two-thirds of patients with DMI are women, with a mean age at presentation of 39 +/- 12 years. The typical clinical presentation includes abrupt onset of thigh pain and tenderness. There is a palpable, painful mass, with swelling and induration of the surrounding tissue without systemic symptoms or signs. The painful lesion persists for weeks, occasionally with exacerbations of symptoms, then spontaneously resolves over several weeks to months. Recurrent episodes are reported in half of the patients. Muscles commonly affected are the vastus lateralis, thigh adductors, and biceps femoris; but calf muscles may be involved as well. Active pathologic changes in the muscle are more sensitively evaluated with T2-weighted sequences on magnetic resonance (MR) imaging, which shows high intensity in involved muscle. Histologic features of DMI consist of large areas of muscle necrosis and edema. Regenerating muscle fibers and lymphocytic interstitial infiltration may be present. CONCLUSION: Diabetic muscular infarction is a rare complication of diabetes mellitus. In most patients, the diagnosis can be made when the characteristic clinical presentation is combined with a typical MR imaging results. Muscle biopsy can be helpful in establishing the diagnosis of DMI, but histologic findings are not specific. Awareness of this syndrome plus MR imaging as the first diagnostic test should lead to the correct diagnosis and shorter hospitalization.
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The authors describe the clinical characteristics and response to therapy of seven patients with hyperthyroidism, dilated cardiomyopathy, and low-output cardiac failure. All patients (4 women and 3 men, age 47 +/- 4 years, mean +/- standard error of the mean) were admitted with the primary diagnosis of congestive heart failure. The cause of hyperthyroidism was Graves' disease in six patients, and toxic multinodular goiter in one. On admission, the mean serum T4 was 21 +/- 1 microgram/dL and mean serum T3:411 +/- 77 ng/mL, and serum thyroid-stimulating hormone was suppressed ( < 0.03 microU/mL) in all patients. Two-dimensional echocardiogram showed biventricular or four chamber dilatation and impaired left ventricular performance. Therapy of heart failure and hyperthyroidism resulted in rapid clinical improvement. During follow-up (5 months to 9 years), left ventricular ejection fraction improved from a mean of 28% to a mean ejection fraction of 55% (P < 0.01). Resolution of dilated cardiomyopathy with normalization of systolic function was achieved in five patients, and improvement from severe to mild left ventricular dysfunction was observed in two patients. We conclude that some patients with hyperthyroidism may have a reversible form of dilated cardiomyopathy and "low-output failure." Assessment of thyroid hormone status in patients with heart failure might permit the identification of patients with dilated cardiomyopathy and thyrotoxicosis who are likely to have reversible cardia dysfunction.
Our preliminary data indicate that 15% of African-American patients presenting with diabetic ketoacidosis (DKA) are obese. To determine underlying mechanisms, we analyzed the clinical characteristics and indexes of insulin secretion and insulin sensitivity in 35 obese patients with DKA, 22 obese patients with hyperglycemia, 10 lean patients with DKA, and 10 obese nondiabetic subjects. Studies were performed 1 day after resolution of DKA and after 12 weeks of follow-up. At presentation, both obese DKA and obese hyperglycemic patients had no detectable insulin response to intravenous glucose, but they did respond to glucagon administration. The acute insulin response (AIR) to glucagon in obese DKA patients (0.9 +/- 0.1 ng/ml, P < 0.01), but significantly greater than in lean patients with DKA (0.1 +/- 0.1 ng/ml, P < 0.01). After 12 weeks of follow-up, the AIR to glucose improved in both groups of obese diabetic patients but remained significantly lower than in nondiabetic control subjects (both P < 0.01). In contrast, the AIR to glucagon was not significantly different from that in obese control subjects. Insulin sensitivity was decreased in both groups of obese diabetic patients at presentation and improved after follow-up to levels similar to those in obese nondiabetic control subjects. Reactivity with islet cell antibodies was not detected in any of the patients. During follow-up, 25 of 35 obese DKA and 16 of 22 hyperglycemic patients were able to discontinue insulin therapy, with continued good metabolic control. Our results indicate that in African-Americans, obese patients with DKA represent a subset of type II diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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Skeletal abnormalities commonly reported in both human and experimental diabetes include impaired linear growth and osteopenia. In the present study we examined the effect of diabetes and insulin therapy on collagen, the major protein constituent of extracellular matrix. Insulin-deficient diabetes was induced in growing rats by injection of 90 mg/kg of streptozotocin. Articular cartilage and long bone (femur) were removed, and tissues incubated with [3H]-proline in vitro for 2 hours at 37 degrees C. Uptake of [3H]-proline into both collagen and noncollagen proteins was determined using purified bacterial collagenase. In cartilage, collagen production decreased to 46% of buffer-injected control animals within one week of induction of diabetes (p less than 0.01), and remained at this level for three weeks. A similar degree of suppression was found in long bone from untreated animals, in which collagen production decreased to 58% of control (p less than 0.01). Insulin administration at the onset of diabetes prevented the expected decrease in collagen production such that after one week of therapy, collagen production in bone and cartilage was 98% and 93% of control (p +/- 0.01 vs. untreated), respectively. When insulin therapy was delayed for one week after the induction of diabetes, collagen production in articular cartilage increased from 46% to 92% and 97% of control at the end of one and two weeks of therapy (p less than 0.01 vs. untreated), respectively. Noncollagen protein production in untreated rats decreased to 49% of control in long bone and to 72% of control in articular cartilage after one week (p less than 0.01), with correction to control levels in both tissues within one week of insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Although changes in collagen production probably play a major role in the connective tissue defects of diabetes, we do not know to what extent these changes are attributable to hormonal/metabolic versus nutritional alterations. To study collagen production as influenced separately by nutrition versus hormonal/metabolic factors, rats were given 50 mg/kg i.v. streptozocin (STZ) (mild weight-gaining diabetes) or 100 mg/kg STZ (severe weight-losing diabetes) and compared with nondiabetic food-restricted rats to match weight changes in diabetic animals. Articular cartilage was incubated with [3H]proline, and uptake of [3H]proline into both collagen and noncollagen proteins was determined with purified bacterial collagenase. Collagen decreased to 49% in mildly diabetic rats and 16% in severely diabetic rats, compared with control rats fed ad libitum and decreased to 85 and 73%, respectively, in food-restricted rats (both P less than .01 vs. diabetes). Diabetes induced a greater defect in collagen production than food restriction and a greater decrease in collagen than noncollagen protein production within each group, suggesting a specific effect on collagen. With comparable levels of metabolic severity (glucose, beta-hydroxybutyrate), diabetic animals that lost weight produced significantly less collagen than animals that gained weight, suggesting separate mechanisms. Quantitation of the impact of undernutrition on collagen production in diabetes demonstrated that approximately 31 to 32% of the defect was due to undernutrition, leaving approximately 68-69% of the defect due to the diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS)
Many of the chronic complications of diabetes mellitus involve defects in the connective tissue such as poor wound healing, diminished bone formation, and decreased linear growth. Because collagen is the major protein component of these connective tissues, we examined collagen production in diabetic rats as a probe of this generalized defect in connective tissue metabolism. Doses of streptozocin ranging from 35 to 300 mg/kg were used to induce diabetes of graded metabolic severity in rats. Parietal bone or articular cartilage was removed and incubated at 37 degrees C with 5 microCi L-[5-3H]proline for 2 h, and collagen and noncollagen protein production were quantitated after separation with purified bacterial collagenase. Within 2 wk after induction of diabetes, collagen production was significantly reduced in bone and cartilage from diabetic rats to 52% (P less than .01) and 51% (P less than .01) of control (buffer-injected) levels, respectively. In contrast, noncollagen protein production in bone and cartilage from diabetic animals was no different from in tissue from control rats. The correlation between collagen relative to total protein production (relative rate) and the degree of hyperglycemia was highly significant for both bone (r = -.77, P less than .001) and cartilage (r = -.87, P less than .001). Other factors found to correlate with altered collagen production were the duration of diabetes and the amount of weight loss. Thus, diabetes is associated with a marked decrease in collagen production, which was seen early after induction of diabetes and was specific when compared with noncollagen protein production. Cumulative effects of these marked changes in collagen production may contribute to the chronic connective tissue complications in diabetes.
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Blood glucose-monitoring techniques originally developed to aid outpatient management of diabetic patients are now being used to facilitate hospital care. However, applications in hyperglycemic patients have been limited because many glucose-oxidase strips and meters respond only to glucose values less than or equal to 400 mg/dl. We asked if prior dilution of blood samples would permit reliable estimations. Ten consecutive decompensated diabetic patients (age 35-73, glucose 506-879, HCO3 12-28) had blood glucose determinations done simultaneously by the hospital laboratory and by Chemstrip bG after dilution of heparinized blood 1:2 in saline. Thirty-one samples were obtained before and during insulin therapy. Correlations with laboratory glucose values were 0.95 with strips read by Accu-Chek meter and 0.90 read visually, both P less than 0.001. Average deviations from laboratory values were 7.9% with Accu-Chek and 12.9% with visual readings. Accu-Chek deviations averaged 9.6% for glucose greater than 700 mg/dl, and 6.9% for glucose greater than 400 mg/dl. Over the first hour of insulin therapy, glucose fell 150 +/- 30 mg/dl by Accu-Chek, comparable to 168 +/- 29 by laboratory measurement; the decrement by visual reading was 107 +/- 32, not significantly different. We conclude that dilution of blood samples with glucose greater than 400 allows reliable estimation of elevated values by home glucose-monitoring techniques. This approach is cost-effective and provides the rapid feedback needed for the management of critically ill patients.