Polyneuropathy with impaired glucose tolerance: Implications for diagnosis and therapy

Opinion statement Prediabetes is associated with a length-dependent polyneuropathy that typically is sensory predominant and painful. A diagnosis of prediabetes should be sought in patients with otherwise idiopathic sensory-predominant neuropathy by doing a 2-hour oral glucose tolerance test. Fasting plasma glucose of 100 to 125 mg/dL or 2-hour glucose 140 to 199 mg/dL (impaired glucose tolerance) constitutes prediabetes. Most patients with neuropathy associated with prediabetes (NAP) are obese and show metabolic manifestations of insulin resistance, including hyperlipidemia and hypertension. Appropriate treatment addresses hyperglycemia, insulin resistance, and neuropathic pain. Professionally administered individualized diet and exercise counseling (modeled on the Diabetes Prevention Program) has been shown to be more effective than glucose-lowering medications in preventing progression from impaired glucose tolerance to diabetes, and is the mainstay of treatment for all patients with NAP. The goals of this therapy should be a 5% to 7% reduction in weight and an increase to 30 minutes of moderate exercise five times weekly. Patients with prediabetes are at increased risk for myocardial infarction, stroke, and peripheral vascular disease. Therefore, risk reduction with control of hypertension and hyperlipidemia is essential. Neuropathic pain troubles nearly every patient with NAP, and often limits aerobic exercise. No trials have specifically addressed the patient population with NAP, and neuropathic pain treatment closely follows recommendations for diabetic neuropathy. Gabapentin, lamotrigine, and tricyclic antidepressants are well-validated first-line therapies. Adjunctive therapy with opioids, nonsteroidal anti-inflammatory drugs often are necessary. Diet and exercise seem to reduce neuropathic pain in patients with NAP.     

Insulin resistance is a common denominator of post-transplant diabetes mellitus and impaired glucose tolerance in renal transplant recipients

Background. Post-transplant diabetes mellitus is a known complication of steroid therapy in renal transplant recipients. Both insulin resistance and insulin deficiency have been shown to be necessary for development of post-transplant diabetes mellitus. It is not known whether recipients with impaired glucose tolerance have similar degree of insulin resistance or deficient insulin response as recipients with post-transplant diabetes mellitus. Methods. To address this question, we used an oral glucose tolerance test to categorize 46 renal transplant recipients on triple immunosuppressive medication to groups with normal glucose tolerance, impaired glucose tolerance or post-transplant diabetes mellitus. Insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp. Insulin response was calculated from the increase in serum insulin concentration during the oral glucose tolerance test. Results. Twenty-five were categorized to normal glucose tolerance, 15 to impaired glucose tolerance and six to post-transplant diabetes mellitus. There were no statistically significant differences between the groups regarding prednisolone dose, azathiprine dose, use of {beta}-blocker, age, gender, weight, waist-hip ratio, body mass index, donor source, smoking habits, or first-degree relatives with histories of diabetes mellitus. The impaired glucose tolerance and post-transplant diabetes mellitus groups showed a significant reduction in insulin-stimulated glucose disposal rate (mg/kg^.min) compared to the normal glucose tolerance group (4.6±1.6 and 3.4±1.3 respectively vs 7.1±2.4, P<0.05). The insulin response (picomol/l) was not different between the normal glucose tolerance and impaired glucose tolerance groups but was significantly reduced in the post-transplant diabetes mellitus group (448±310 and 450±291 respectively vs 170±128, P<0.05).Conclusion. Insulin resistance is a common denominator of post-transplant diabetes mellitus and impaired glucose tolerance in renal transplant recipients.     

Management of Hyperglycemia in Acute Ischemic Stroke

There is considerable clinical evidence that hyperglycemia at the onset of acute ischemic stroke may negatively impact not only acute morbidity but also brain recovery. Establishing hyperglycemia treatment protocols is challenging, given the variation among patients and acute stroke care settings. Relatively few randomized trials have examined glycemic control protocols in this population, and there is not yet any clear evidence that “correcting” hyperglycemia in patients with acute stroke leads to better functional outcomes. Intensification of glucose regimens, using lower glucose targets, leads to more hypoglycemic events, but the immediate and long-term impact of these events on the acutely ischemic brain is unknown. It is reasonable to treat patients with acute ischemic stroke according to the American Diabetes Association inpatient glycemic control guidelines, initiating therapy to achieve glucose targets of 140 to 180 mg/dL if fasting glucose is greater than 140 mg/dL or random glucose is consistently higher than 180 mg/dL. Lower glucose targets (<140 mg/dL) may be appropriate for patients with well-controlled diabetes and those with stress hyperglycemia who were not known to be diabetic before admission, but glucose levels less than 80 mg/dL should be avoided. Patients who present with extreme or persistent hyperglycemia, are critically ill, or who are treated with thrombolytic therapy should be started on an established and standardized intravenous insulin protocol to improve blood glucose control for at least the first 24 to 48 h of hospitalization. They should then be transitioned to a subcutaneous insulin regimen that includes basal long-acting insulin along with correction rapid-acting insulin for glucose that is out of range. Prandial (meal) insulin should be added for patients who are eating; this would preferably be a rapid-acting insulin analogue that can be administered immediately before or after the meal. Caution and close glucose monitoring are necessary, especially for patients prone to hypoglycemia, such as those with type 1 diabetes mellitus or hepatic or renal impairment, or those on complicated feeding regimens.     

Risk factors for the development of new-onset diabetes mellitus in a living related renal transplant program

New-onset diabetes mellitus is associated with considerable morbidity after transplantation. We evaluated 78 living related renal transplant recipients due to all causes except diabetic nephropathy a waiting a living related renal transplantation. We evaluated demographic characteristics, pretransplant glycemic profile, fasting C-peptide levels, plasma insulin levels, pretransplant insulin resistance, and immunosuppression protocols. Among the 16.7% of patients developing diabetes mellitus at the end of 1 year, age, family history, and impaired glucose tolerance at the time of transplantation corelated with the development of diabetes mellitus in the posttransplant period.     

Combination therapy of pioglitazone with voglibose improves glycemic control safely and rapidly in Japanese type 2-diabetic patients on hemodialysis

AIMS: Unfortunately, clinicians are diagnosing a growing number of patients on hemodialysis (HD) with insulin-resistant, Type 2 diabetes in Japan. While alpha-glucosidase inhibitors (alpha-GI) such as oral antidiabetic agents are indicated for Japanese diabetics on HD, pioglitazone and other PPARgamma agonists are now contraindicated. No prospective study has evaluated the use of thiazolidinediones in diabetics with end-stage renal disease (ESRD) in combination with alpha-GI. In this study we evaluated the efficacy and safety of pioglitazone in Japanese diabetics on HD. METHODS: An open-label randomized study was performed on 31 Type 2 diabetics on HD with unstable glycemic control receiving constant doses of voglibose. The patients were randomly assigned to two groups: a combination therapy group (pioglitazone group) administered pioglitazone (fixed dose 30 mg) plus voglibose, and a monotherapy group (control group) administered voglibose alone. The efficacy of the treatments was determined by monitoring glycemic control (plasma glucose and HbA1c) and insulin resistance. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-R). Safety and tolerance were determined by monitoring clinical and laboratory parameters. RESULTS: The pioglitazone was effective in reducing plasma glucose and HbA1c from the baseline levels from Week 4 onward. It was also effective in reducing triglycerides. HOMA-R decreased significantly at 4 weeks in the pioglitazone group, and the decrease continued up to the last measurement at Week 12. Systolic and diastolic blood pressures at 4 weeks were statistically lower in the pioglitazone group than in the control group. No serious adverse effects such as hypoglycemia, liver impairment or rhabdomyolysis were observed in any of the patients. CONCLUSIONS: Pioglitazone was safe and effective as a treatment for diabetics on dialysis therapy. The 30 mg daily dose of pioglitazone was sufficient for Japanese HD patients, obese and nonobese alike. The combination therapy of pioglitazone with voglibose will add to the list of first-line drug treatments for glycemic control in uremic Type 2 diabetes.     

Insulin resistance in African Americans

Hypertension and diabetes mellitus are the leading contributors to end-stage renal disease. African Americans suffer higher rates of renal failure as well as other vascular morbidities associated with hypertension and diabetes. Insulin resistance is strongly associated with hypertension. Insulin resistance is a component of diabetes and also precedes the clinical expression of type 2 diabetes. The relationship of blood pressure with insulin resistance, or impaired insulin action, occurs in African Americans and can be detected at young ages prior to the clinical expression of hypertension or diabetes. Through its relationship with hypertension, diabetes, and hyperlipidemia, insulin resistance is associated with endothelial dysfunction. The interface of insulin resistance with endothelial dysfunction may begin to explain the role of insulin resistance in vascular and renal pathology. The injury process, subsequent to both hypertension and diabetes, appears to be mediated by alterations tissue regulatory factors, and include vasoactive peptides such as angiotensin II, endothelin, and growth factors. Understanding the determinants that up-regulate the aberrant pathways and the early phases of these processes will be necessary to formulate strategies to effectively achieve renal protection and reduce the rates of renal failure in African Americans.     

Perioperative management of diabetic patients

Diabetes mellitus is the most common metabolic disease. New classifications have recently been proposed by the American Diabetes Association (ADA) and the World Health Organization (WHO). Type 1 (formerly insulin-dependent diabetes mellitus IDDM) is immune-mediated and leads to absolute insulin deficiency. Type 2 diabetes (formerly non-insulin-dependent diabetes mellitus [NIDDM]) is a disease of adult onset and is associated with insulin resistance. Type 3 corresponds to a wide range of specific types of diabetes, including various genetic defects of beta-cell function and insulin action, diseases of exocrine pancreas, endocrinopathies, and drug-induced diabetes. Type 4 is gestational diabetes (Table 1). Diabetics undergoing surgery have increased mortality, and type 1 diabetics are particularly at risk of postoperative complications. Wound complications are increased in diabetics, and healing is severely impaired when glycemic control is poor. However, with the use of modern management plans, the major outcome measures of surgery are comparable in diabetic and nondiabetic patients. Successful management of surgery in diabetic patients requires simple and safe protocols, which are fully understood by all staff and a close liaison among the surgeons, diabetes care team, and anesthetists. There is no consensus on the optimal metabolic management of the diabetic patient during surgery. Several surveys have highlighted the inconsistency with which surgical problems are managed in diabetic patients. The aim of this article is to provide protocols to achieve sensible and practical glycemic control in diabetic patients undergoing surgery.     

Insulin therapy for maximal glycemic control in type 2 diabetes mellitus

Type 2 diabetes mellitus is on the rise, yet glycemic control continues to elude patients-and their physicians. During the past decade, the use of insulin monotherapy has decreased while the use of oral antidiabetic agents (either alone or in combination with insulin injections) has increased. The continued prevalence of the disorder, changes in prescribing patterns, and recent data indicating that only one third of patients with type 2 diabetes mellitus achieve glycemic control underscore the need for physicians to reevaluate the clinical management of this now common disorder. Insulin analogs provide flexibility in the delivery of insulin therapy for this population. Although potential barriers and complications to initiation exist, patients should understand that achieving and maintaining glycemic control reduces the risk of long-term complications as a result of type 2 diabetes mellitus. Physicians are encouraged to actively identify and address patient concerns about this treatment modality.     

Effects of long-term optimization and short-term deterioration of glycemic control on glucose counterregulation in type I diabetes mellitus

To assess the effects of glycemic control on glucose counterregulation, rates of plasma glucose recovery from hypoglycemia and counterregulatory hormonal responses were studied in 18 C-peptide-negative patients with insulin-dependent diabetes mellitus (IDDM) before and after either improvement, no change, or deterioration in glycemic control. Hypoglycemia was induced by an i.v. insulin infusion (30 mU/m2 X min for 1 h) after maintenance of euglycemia overnight with i.v. insulin. In 13 patients with long duration of IDDM (9 +/- 0.5 yr, mean +/- SEM) and initially poor glycemic control (mean diurnal blood glucose, MBG 199 +/- 8 mg/dl, ketoamine-HbA1 12.4 +/- 0.2%; nondiabetic subjects 104 +/- 4 mg/dl and 6.8 +/- 0.09%, respectively), rates of plasma glucose recovery from hypoglycemia (0.30 +/- 0.01 versus 0.60 +/- 0.01 mg/dl X min in nondiabetic subjects, P less than 0.001) and plasma glucagon (AUC 0.56 +/- 0.09 versus 6.3 +/- 0.50 ng/ml X 150 min in nondiabetic subjects, P less than 0.01) and epinephrine (AUC 16.9 +/- 0.2 versus 25.7 +/- 0.2 ng/ml X 150 min in nondiabetic subjects, P less than 0.001) responses to hypoglycemia were impaired. Intensive therapy (three daily injections of insulin) instituted in 7 out of 13 IDDM patients for up to 9 mo improved MBG (124 +/- 6 mg/dl, P less than 0.01) and ketoamine-HbA1 (7.9 +/- 0.02%, P less than 0.01) but not rates of plasma glucose recovery (0.31 +/- 0.01 mg/dl X min) and plasma glucagon (AUC 0.69 +/- 0.07 ng/ml X 150 min) and epinephrine (AUC 14.9 +/- 0.17 ng/ml X 150 min) responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased sympathochromaffin activity in IDDM

Catecholamines released from the sympathochromaffin system produce metabolic changes similar to those of diabetes mellitus. However, increased sympathochromaffin activity does not appear to be a feature of insulin-dependent diabetes mellitus (IDDM), although physiologic catecholamine increments may contribute to short-term metabolic derangements under some conditions. Increased glycemic sensitivity to epinephrine is a feature of IDDM but is the result of the inability to secrete insulin rather than of increased cellular sensitivity to catecholamines. Absolute insulin deficiency results in increased metabolic (glycemic, lipolytic, and ketogenic) sensitivity to catecholamines. More generalized hypersensitivity occurs in diabetic autonomic neuropathy. However, the clinical relevance of these alterations in sensitivity remains to be established. On the other hand, decreased sympathochromaffin activity is common and causes considerable morbidity and some mortality in people with diabetes. In addition to increased sensitivity to catecholamines, decreased sympathochromaffin activity results in the clinical syndromes of postural hypotension, hypoglycemia unawareness, defective glucose counterregulation, or a combination of these. The latter two syndromes cause an increased frequency of severe iatrogenic hypoglycemia, at least during intensive therapy of IDDM. Thus, decreased rather than increased sympathochromaffin activity often complicates IDDM. Clearly, ways to prevent, correct, or compensate for this component of diabetic autonomic neuropathy must be learned before diabetes can be managed effectively and safely in all patients who suffer from the disease until diabetes mellitus is eradicated.     

Osteoporosis in patients with diabetes mellitus.

Demographic trends with longer life expectancy and a lifestyle characterized by low physical activity and high-energy food intake contribute to an increasing incidence of diabetes mellitus and osteoporosis. Diabetes mellitus is a risk factor for osteoporotic fractures. Patients with recent onset of type 1 diabetes mellitus may have impaired bone formation because of the absence of the anabolic effects of insulin and amylin, whereas in long-standing type 1 diabetes mellitus, vascular complications may account for low bone mass and increased fracture risk. Patients with type 2 diabetes mellitus display an increased fracture risk despite a higher BMD, which is mainly attributable to the increased risk of falling. Strategies to improve BMD and to prevent osteoporotic fractures in patients with type 1 diabetes mellitus may include optimal glycemic control and aggressive prevention and treatment of vascular complications. Patients with type 2 diabetes mellitus may additionally benefit from early visual assessment, regular exercise to improve muscle strength and balance, and specific measures for preventing falls.     

Magnesium and type 2 diabetes

Type 2 diabetes is frequently associated with both extracellular and intracellular magnesium(Mg) deficits. A chronic latent Mg deficit or an overt clinical hypomagnesemia is common in patients with type 2 diabetes, especially in those with poorly controlled glycemic profiles. Insulinand glucose are important regulators of Mg metabolism. Intracellular Mg plays a key role in regulating insulin action, insulin-mediated-glucose-uptake and vascular tone. Reduced intracellular Mg concentrations result in a defective tyrosine-kinase activity, postreceptorial impairment in insulin action and worsening of insulin resistance in diabetic patients. A low Mg intake and an increased Mg urinary loss appear the most important mechanisms that may favor Mg depletion in patients with type 2 diabetes. Low dietary Mg intake has been related to the development of type 2 diabetes and metabolic syndrome. Benefits of Mg supplementation on metabolic profiles in diabetic patients have been found in most, but not all clinical studies and larger prospective studies are needed to support the potential role of dietary Mg supplementation as a possible public health strategy in diabetes risk. The aim of this review is to revise current evidence on the mechanisms of Mg deficiency in diabetes and on the possible role of Mg supplementation in the prevention and management of the disease.     

Effect of Liver Transplantation on Glucose Levels in Patients with Prediabetes or Type 2 Diabetes

Background

Liver transplantation (LT) may induce the occurrence of diabetes mellitus. It can be speculated, however, that the LT may have a beneficial effect on glucose metabolism. We therefore conducted a study to examine the changing trends in blood glucose levels before and after LT in patients with prediabetes or type 2 diabetes.

Methods

In this observational study, we enrolled 47 patients (38 prediabetes and 9 diabetes) who underwent LT. We compared the blood glucose levels between the pre-transplantation (24 months) and the post-transplantation (36 months) periods and analyzed the diverse factors affecting glucose levels.

Results

The glucose regulation worsened and insulin dose increased in patients with diabetes, which was notably seen during the steroid maintenance period. Following steroid withdrawal, however, there was a decrease in the insulin dose in 55.6% of the patients, and 33.3% of the patients converted from insulin to oral agents. Of the patients with prediabetes, 55.3% developed new-onset diabetes after transplantation (NODAT). However, 18.4% achieved a recovery of glucose levels to normal range. Of the 21 NODAT patients, 52.4% achieved a recovery of glucose level to the prediabetes range after steroid withdrawal. There was a significant correlation between the old age and the persistence of NODAT (P < .05).

Conclusions

LT may have a diverse effect on glycemia, which may lead to changes in glucose control methods. Therefore, glucose metabolism after LT may need to be differentiated by the underlying glucose disturbance status and the time after LT with or without steroid maintenance period.     

糖尿病患者手术前糖耐量及C肽检测分析

目的 :探讨糖尿病患者择期手术前糖耐量、胰岛素、C肽释放试验对糖尿病的诊断价值。 方法 :共检测择期手术前 565例糖尿病患者 ,葡萄糖耐量异常 67人 ,正常 96人。 结果 :Ⅰ型糖尿病患者胰岛素、C肽分泌显著低于正常对照组 (P<0 0 1) ,胰岛素、C肽分泌呈低平曲线 ;Ⅱ型糖尿病患者胰岛素、C肽空腹值正常 ,但分泌高峰明显后延且持续时间长 (P <0 0 1) ;糖耐量异常患者达峰值时间在对照组与Ⅱ型糖尿病之间。 结论 :糖尿病患者手术前的检查及有效治疗可提高手术的安全性 ,减少术后并发症     

The dynamics of glucose metabolism under calcineurin inhibitors in the first year after renal transplantation in nonobese patients

BACKGROUND: The incidence of glucose metabolism disturbances after transplantation often is based on the use of hypoglycemic agents and not on the results of glucose tolerance tests (GTTs), which may camouflage the real incidence. A lack of information also exists regarding the profile of glucose metabolism during the first year after transplant. METHODS: Oral GTT along with insulin measurements and drugs pharmacokinetics were prospectively performed at days 30, 60, 180, and 360 after transplant to diagnose disturbances of glucose metabolism after renal transplantation, in nonobese patients receiving either tacrolimus (n=55) or cyclosporine (n=29), along with mycophenolate mofetil and steroids. RESULTS: The incidence of impaired glucose tolerance or diabetes mellitus reached a peak at 60 days and decreased at 1 year. It could not be adequately diagnosed using fasting plasma glucose in a decreased abnormal (>99 ng/mL) range. In both groups, insulin secretion, evaluated by the Homeostasis Model Assesment (HoMA-beta), decreased (P<0.005) from the condition of normal GTT (101+/-56%) to impaired glucose tolerance (72+/-35%) and diabetes mellitus (54+/-25%). In the cyclosporine group, insulin secretion was normal and stable throughout the study period, but in the tacrolimus group, insulin secretion recovered over time and was inversely correlated with tacrolimus exposure. Insulin resistance (HoMA-IR) did not change. CONCLUSIONS: This study shows the need to perform an oral GTT at 60 days and at the end of the first year of renal transplantation to adequately diagnose impaired glucose metabolism.     

Effect of glyburide on glycemic control, insulin requirement, and glucose metabolism in insulin-treated diabetic patients

Glycemic control and glucose metabolism were examined in 5 patients with insulin-dependent diabetes mellitus (IDDM) and 8 insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients before and after 2 mo of therapy with glyburide (20 mg/day). Glycemic control was assessed by daily insulin requirement, 24-h plasma glucose profile, glucosuria, and glycosylated hemoglobin. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, and insulin sensitivity was determined by a two-step euglycemic insulin clamp (1 and 10 mU X kg-1. X min-1) performed with indirect calorimetry and [3-3H]glucose. In the IDDM patients, the addition of glyburide produced no change in daily insulin dose (54 +/- 8 vs. 53 +/- 7 U/day), mean 24-h glucose level (177 +/- 20 vs. 174 +/- 29 mg/dl), glucosuria (20 +/- 6 vs. 35 +/- 12 g/day) or glycosylated hemoglobin (10.1 +/- 1.0 vs. 9.5 +/- 0.7%). Furthermore, there was no improvement in basal hepatic glucose production (2.1 +/- 0.2 vs. 2.4 +/- 0.1 mg X kg-1 X min-1), suppression of hepatic glucose production by low- and high-dose insulin infusion, or in any measure of total, oxidative, or nonoxidative glucose metabolism in the basal state or during insulin infusion. C-peptide levels were undetectable (less than 0.01 pmol/ml) in the basal state and after glucagon infusion and remained undetectable after glyburide therapy. In contrast to the IDDM patients, the insulin-treated NIDDM subjects exhibited significant reductions in daily insulin requirement (72 +/- 6 vs. 58 +/- 9 U/day), mean 24-h plasma glucose concentration (153 +/- 10 vs. 131 +/- 5 mg/dl), glucosuria (14 +/- 5 vs. 4 +/- 1 g/day), and glycosylated hemoglobin (10.3 +/- 0.7 vs. 8.0 +/- 0.4%) after glyburide treatment (all P less than or equal to .05). However, there was no change in basal hepatic glucose production (1.7 +/- 0.1 vs. 1.7 +/- 0.1 mg X kg-1 X min-1), suppression of hepatic glucose production by insulin, or insulin sensitivity during the two-step insulin-clamp study. Both basal (0.14 +/- 0.05 vs. 0.32 +/- 0.05 pmol/ml, P less than .05) and glucagon-stimulated (0.24 +/- 0.07 vs. 0.44 +/- 0.09 pmol/ml) C-peptide levels rose after 2 mo of glyburide therapy and both were correlated with the decrease in insulin requirement (basal: r = .65, P = .08; glucagon stimulated: r = .93, P less than .001).(ABSTRACT TRUNCATED AT 400 WORDS)     

Islet transplantation in the future: Use of a bioartificial pancreas

Tight glycemic control effectively delays the onset and slows the progression of diabetic complications in patients with insulin-dependent diabetes mellitus. Successful pancreas transplantation corrects abnormal glucose metabolism but subjects patients to morbidity and mortality associated with chronic immunosuppression. Immune exclusion devices containing pancreatic islets (bioartificial pancreas devices) are designed to provide glycemic control through islet transplantation without immunosuppression. The immune exclussion is achieved by separating allogeneic or xenogeneic islets from the host by semipermeable membranes that allow only small molecules, such as glucose, insulin, and nutrients, to pass through. Immune lymphocytes and immunoglobulins are excluded by the membrane and are unable to cause destruction of the islets. This report provides a brief review of three types of bioartificial pancreas devices used for the treatment of diabetes, i.e., perfusion-based vascular devices, diffusion-based chambers and microcapsules, and describes recent progress in each area.     

Diabetes mellitus in patients with infantile cystinosis after renal transplantation

Diabetes mellitus is a frequent long-term complication of infantile nephropathic cystinosis. We studied 44 cystinotic patients, aged 22.1±5.4 years, transplanted at a mean age of 11.3±2.5 years; 25% were treated with insulin at 20 years of age or 10 years after transplantation, and over half required insulin at latest follow-up. In comparison, diabetes mellitus occurred in only 1% of non-cystinotic transplanted patients. Sequential oral glucose tolerance tests (OGTTs) in these patients showed the progressive deterioration of glucose metabolism. All but 2 patients had an abnormal response at latest follow-up. The high doses of corticosteroid given after transplantation or during rejection episodes were responsible for transient insulin dependency. However, the development of impaired glucose tolerance and diabetes mellitus depended mainly on the cystinotic process, which developed slowly with time. The deterioration of glucose tolerance was correlated with a decreased early phase of insulin secretion, estimated from the plasma insulin level at 30 min of the OGTT, while there was no evidence of insulin resistance. The occurrence of diabetes mellitus correlated with a worsening of the vital prognosis. Received: 28 July 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998     

Effects of tolazamide and exogenous insulin on pattern of postprandial carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus. Results of randomized crossover trial

To determine whether therapy with exogenous insulin or sulfonylureas results in a postprandial pattern of carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM) that resembles that in nondiabetic individuals, we employed a dual-isotope technique combined with forearm catheterization to examine meal disposition in NIDDM patients, before and after 3 mo of therapy with tolazamide and after 3 mo of therapy with exogenous insulin, with a randomized crossover design. Results were compared with those observed in nondiabetic subjects. Although both forms of therapy improved chronic glycemic control (glycosylated hemoglobin concentration went from 9.6 +/- 0.7 to 7.6 +/- 0.5 and 7.1 +/- 0.2%, respectively, P less than .01), exogenous insulin resulted in a lower postprandial glycemic response than tolazamide (P less than .001). Both agents comparably increased (P less than .01) fasting and integrated postprandial insulin concentrations. However, the initial rate of postprandial increase was greater with exogenous insulin (P less than .05). Tolazamide (P less than .05) but not exogenous insulin increased postprandial C-peptide concentrations. However, tolazamide did not improve the deficient early insulin release. Both agents (P less than .05) lowered postabsorptive hepatic glucose release (from 2.8 +/- 0.3 to 2.3 +/- 0.2 mg . kg-1 . min-1), but not to normal rates (1.8 +/- 0.1 mg . kg-1 . min-1).(ABSTRACT TRUNCATED AT 250 WORDS)