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PubMed1982

Acute effect of prednisone and deflazacort on glucose tolerance in prediabetic subjects.

The diabetogenic effect of deflazacort (DF), an oxazolinic synthetic corticosteroid, was studied in 12 healthy adult subjects with a positive family history of diabetes mellitus. Three oral glucose tests (oGTT) were performed at 9.00 a.m., after a 12 h fast, following randomized administration of Placebo (PL), or Deflazacort (DF 36 +36 mg) or Prednisone (PN 30 + 30 mg) 12 and 2 h before the test. Plasma glucose (BG), insulin (IRI), non-esterified fatty acids, (NEFA), total cholesterol (CL), HDL-cholesterol (HDL-CL) and triglycerides (TG) were measured at time 0, and BG, IRI, NEFA were again measured 30, 60, 90 and 120 min after oGTT. PN was followed by a significant increase in BG over the PL values in accordance with the prediabetic state of these subjects, and there was also an increase in IRI values. No change in CL, HDL-CL and TG was found. AFter DF administration, there was a small increase only in BG and IRI over PL values. The differences between DF- PL were not significant, but those between PL-PN and DF-PN were significant at p less than 0.05 (Scheffe's test). The lesser metabolic effect of DF on glucose balance by comparison with PN, as shown by these results, is consistent with previous reports of its lower osteopaenic effect. Thus, DF may be more suitable than PN and similar corticosteroids for corticosteroid therapy in prediabetic and diabetic subjects.

Adult↗

PubMed2003

Incidence, coronary risk profile and angiographic characteristics of prediabetic and diabetic patients in a population with ischemic heart disease.

BACKGROUND: Recently, the threshold of fasting blood glucose indicating diabetes mellitus was lowered to 7.00 mmol/L (126 mg/dL) and the term 'impaired fasting glucose' (IFG; fasting blood glucose ranging from 6.11 mmol/L to 6.99 mmol/L or from 110 mg/dL to 126 mg/dL) was introduced to define a prediabetic state. OBJECTIVE: To evaluate the incidence of the above states in a Canadian population with suspected coronary artery disease and to compare their risk profiles and angiographic status to normoglycemic subjects. PATIENTS AND METHODS: Revision of the database of 1108 consecutive patients (793 males and 315 females; mean age 58.1+/-9.8 years) undergoing clinical, biochemical and elective angiographic studies because of suspected coronary artery disease. RESULTS: One third of the patients had either IFG (8.5%), or were diabetics (24.2%). Unlike the 747 normoglycemic patients, both IFG (n=94) and diabetic (n=267) subjects showed an insulin resistance profile, with abdominal obesity, and dislipidemia characterized by high triglycerides in the presence of low high density lipoprotein-cholesterol and high normal or elevated blood pressure. Both prediabetics and diabetics had a significantly higher homeostatic model assessment insulin resistance index than normoglycemics (P<0.0001), the index also being higher for diabetics than for prediabetics (P<0.0001). Coronary atherosclerosis was documented in most patients of the three groups and was significantly more severe in diabetics than in IFG patients (P=0.0359) or normoglycemics (P=0.0069), with no differences between the former two groups. CONCLUSIONS: As expected, the new definitions identify more patients with impaired homeostasis than earlier criteria. IFG patients have similar coronary risk profile as diabetics, suggesting the need for similar coronary precautions.

Aged↗

PubMed1976

Mean retinal circulation time as determined by fluorescein angiography in normal, prediabetic, and chemical-diabetic subjects.

A preliminary survey has been completed using manual densitometric technics to determine the mean retinal circulation times in groups of normal controls, offspring to two diabetic parents with normal glucose tolerance (prediabetics), and offspring of two diabetic parents with abnormal glucose tolerance (chemical diabetics). Comparisons of the mean retinal circulation time showed differences between the left eye and right eye in prediabetic and chemical diabetic groups and a sex difference in both normals and prediabetics. In addition, both age and per cent ideal body weight were inversely related to the mean retinal circulation time. The levels of fasting serum cholesterol, triglyceride, and growth hormone, in many instances, also appeared to be inversely related to the mean retinal circulation time. Similarly, the degree of glucose tolerance (determined by the area under the glucose curve above baseline) was significantly inversely related to the mean retinal circulation time. The mean retinal circulation time adjusted for per cent ideal weight was analyzed separately for both right eye and left eye, and a significantly shorter mean retinal circulation time was noted, particularly in males, for prediabetics than for normal controls and for chemical diabetics than for both prediabetics and normals. Analysis of the mean retinal circulation time adjusted for age showed similar differences. It is postulated that the genetic prediabetic state with or without glucose intolerance might be associated with significant alterations of mean retinal circulation time independent of age and per cent ideal weight. It is also suggested that a number of potentially meaningful interrelationships between the degree of glucose intolerance and/or hyperlipidemia might exist and should be further quantified.

Adult↗

PubMed2004

Upregulation of vascular ET(B) receptor gene expression after chronic ET(A) receptor blockade in prediabetic NOD mice.

In the aorta of prediabetic non-obese diabetic mice, a model of human type 1 diabetes, we investigated gene expression of the endothelin receptors and contractility to big endothelin-1 and endothelin-1 at the ages of 10 and 16 weeks. A subgroup of 10- week-old animals was treated with the endothelin ETA receptor antagonist LU461314 (30 mg/kg per day for 6 weeks). Blood glucose levels were normal in all animals. Real-time polymerase chain reaction analysis revealed that vascular ETB receptor expression was higher in 10-week-old non-obese diabetic (NOD) mice compared with controls. In 16-week-old NOD mice, but not in control mice, ETB receptor mRNA was twofold lower (P < 0.05 vs 10-week-old NOD mice). In all groups ETA receptor expression was unaffected by age or treatment. Contractions to big endothelin-1 and endothelin-1 were lower in 10-week-old NOD mice compared with controls. Treatment with LU461314 increased ETB receptor expression in 16-week-old NOD mice, but had no effect on vascular contractility. These data indicate that dysregulation of ETB receptor expression and a decreased contractile response to big endothelin-1 and endothelin-1 are present in the prediabetic state of a model of human type 1 diabetes. These alterations occur independent of glucose levels. Furthermore, ETA receptor blockade is effective in increasing ETB receptor gene expression, suggesting a potential role for endothelin ETA antagonists in the treatment of type 1 diabetes.

Age Factors↗

PubMed2006

Therapy insight: neurological complications of prediabetes.

Stroke and peripheral neuropathy are recognized neurological complications of diabetes. Increasing epidemiological evidence also implicates the prediabetic state of impaired glucose tolerance (IGT) as a risk factor for cerebrovascular events and peripheral neuropathy. Data linking IGT to cognitive decline or deficits, however, are less robust. IGT is one component of metabolic syndrome, together with central obesity, hypertension, hypertriglyceridemia and reduced HDL. Each component of metabolic syndrome is an independent risk factor for stroke, but hyperglycemia might be more important than other components in the pathogenesis of neuropathy. Goal-driven diet and exercise regimens, together with pharmacological treatment of hyperlipidemia and hypertension, reduce stroke risk, but the effect of these interventions on neuropathy has not been fully explored.

Cognition Disorders↗

PubMed2006

Animal models of type 2 diabetes: clinical presentation and pathophysiological relevance to the human condition.

The prevalence of diabetes throughout the world has increased dramatically over the recent past, and the trend will continue for the foreseeable future. One of the major concerns associated with diabetes relates to the development of micro- and macrovascular complications, which contribute greatly to the morbidity and mortality associated with the disease. Progression of the disease from prediabetic state to overt diabetes and the development of complications occur over many years. Assessment of interventions designed to delay or prevent disease progression or complications in humans also takes years and requires tremendous resources. To better study both the pathogenesis and potential therapeutic agents, appropriate animal models of type 2 diabetes (T2D) mellitus are needed. However, for an animal model to have relevance to the study of diabetes, either the characteristics of the animal model should mirror the pathophysiology and natural history of diabetes or the model should develop complications of diabetes with an etiology similar to that of the human condition. There appears to be no single animal model that encompasses all of these characteristics, but there are many that provide very similar characteristics in one or more aspects of T2D in humans. Use of the appropriate animal model based on these similarities can provide much needed data on pathophysiological mechanisms operative in human T2D.

Animals↗

PubMedDate not supplied

[Study of glucose tolerance disorder in women with a complicated obstetrical anamnesis].

The authors examined selectively 849 women with complicated obstetrical anamnesis in the past and at random 636 women with the aid of the glucose tolerance test (GTT). The incidence of pathological GTT among women with various types of pathology of pregnancy (24%) was greater than in the control group (16.9%). Diabetes mellitus was revealed in 7.8 and 5.1% of cases, respectively. Some types of pathology of pregnancy were of particular significance in the development of the prediabetic state. A high incidence of GTT of diabetic type was noted in women with perinatal death of the fetus (13.1%) and the neonate (11.8%), in women with a large fetus in combination with other types of pathology of pregnancy (12.6%), and also among women who had delivered three and more large fetuses in the past (19.5%). The incidence of diabetic GTT increased in older and obese women; in marked excess of body weight the percentage of GTT of diabetic type was about the same in all the women under study. Among the women with pathology of pregnancy adiposity developed more frequently and in younger persons, and the excess of body weight was much greater in comparison with the control group. The authors consider that GTT should be conducted in all the women with the mentioned pathology of pregnancy in the anamnesis for the purpose of early detection of diabetes mellitus and also for perinatal fetal protection.

Adult↗

PubMed2005

Glucose intolerance in young TallyHo mice is induced by leptin-mediated inhibition of insulin secretion.

The pathophysiology of TallyHo mouse, a recently established animal model for type 2 diabetes mellitus, was analyzed at prediabetic state to examine the inherent defects which contribute to the development of diabetes. At 4 weeks of age, the TallyHo mice already revealed glucose intolerance while their peripheral tissues exhibited normal insulin sensitivity. On the other hand, decreased plasma insulin concentration was observed with little differences in pancreatic insulin contents, indicating the impaired insulin secretion. Such defect, however, was not found in the isolated islets, which suggests a role of endocrine factor in impaired insulin secretion of TallyHo mice. Treatment of leptin inhibited the glucose-stimulated insulin secretion from the isolated islets of TallyHo mice, while in vivo administration of anti-leptin antibody lowered plasma glucose concentration with increased insulin level in TallyHo mice. Expression of glucokinase mRNA was decreased both in whole pancreas and leptin treated islets of TallyHo mice compared with whole pancreas in C57BL/6 mice and untreated islets of TallyHo mice, respectively. These results suggest that elevated plasma leptin can, through the inhibition of insulin secretion, induce glucose intolerance in TallyHo mice.

Animals↗

PubMed1988

Low acute insulin response to intravenous glucose. A sensitive but non-specific marker of early stages of type 1 (insulin-dependent) diabetes.

Preventive treatment of Type 1 (insulin-dependent) diabetes presupposes early and accurate diagnosis of prediabetic states. The low acute insulin response to intravenous glucose has been proposed as a marker of both pre-Type 1 and pre-Type 2 (non-insulin-dependent) diabetes. In order to test the reliability of this marker for clinical detection of Type 1 diabetes we looked for this anomaly in 150 first degree relatives of Type 1 diabetic patients, 31 relatives of Type 2 diabetic patients and 39 young non-obese diabetic patients with mild or transient hyperglycaemia. The low acute insulin response was defined by a peak insulin value (sum of plasma insulin at 2 and 5 min after glucose load, 0.3 g/kg body weight) below 50 microU/ml. It was observed in 12% of the relatives of Type 1 diabetic patients (2 of them became diabetic) and in 13% of the relatives of Type 2 diabetic patients. Reproducibility of the peak insulin value in 2 subsequent tests (r = 0.749) was inadequate to interpret small variations in one individual. In the population of 39 diabetic patients, 10 subsequently developed typical Type 1 diabetes, 9 were low insulin responders. In the 29 patients who are still non-insulin-dependent 3 years later, the anomaly was found in the 3 islet cell antibody-positive subjects and 11 out of 26 patients with no detectable antibodies. In conclusion, low acute insulin response to glucose is a sensitive but non-specific marker of early stages of Type 1 diabetes as this anomaly is shared by both Type 2 and Type 1 diabetes.

Adolescent↗

PubMed1996

Prediabetic markers in children with stress hyperglycemia.

BACKGROUND: Previous studies have shown that children with stress hyperglycemia have an increased risk for development of type I or insulin-dependent diabetes mellitus. OBJECTIVE: To determine whether stress hyperglycemia in prospectively screened pediatric patients represents a prediabetic state. DESIGN: Prospective, cohort analytic study. SETTING: The Children's Hospital of the King's Daughters is an urban pediatric emergency department at a tertiary care, university-based children's hospital in Norfolk, Va. PATIENT POPULATION: All patients who required a venipuncture for evaluation of an acute illness or injury from October 1992 through March 1993 were screened prospectively for hyperglycemia (blood glucose level > or = 8.3 mmol/L [> or = 150 mg/dL]). Each hyperglycemic patient was age matched to a stress control subject (defined as a nonhyperglycemic but acutely ill child) from the emergency department and a healthy control subject from a well-child clinic. INTERVENTION: Blood samples were obtained at the time of initial evaluation in the emergency department from 30 hyperglycemic patients (age range, 4 weeks to 12.4 years; median, 2 years), 30 stress control subjects, and 30 healthy control subjects. All samples were tested for islet cell antibodies, insulin autoantibodies, glutamic acid decarboxylase (GAD) antibodies, and HLA typing, specifically the genotypes at the DQB1 gene. MAIN OUTCOME MEASURES: The presence of immunologic or genetic markers for insulin-dependent diabetes mellitus and/or the clinical development of insulin-dependent diabetes mellitus. RESULTS: No patients or control subjects were positive for islet cell antibodies. One hyperglycemic patient and 3 stress control subjects were positive for insulin autoantibodies; all 4 of these subjects had sickle-cell disease and fever. Four of the 8 patients with sickle-cell disease had insulin autoantibodies, compared with none of the 52 patients and stress control subjects without sickle-cell disease (P < .001). One healthy control subject had antibodies to GAD65. The patient group did not show increased genotypes at the DQB1 gene that were indicative of an enhanced risk for insulin-dependent diabetes mellitus. Of the 32 hyperglycemic patients, 27 healthy control subjects, and 25 stress control subjects contacted for follow-up at 31 to 36 months, none has developed insulin-dependent diabetes mellitus. CONCLUSIONS: Children with stress hyperglycemia do not have an increased prevalence of immunologic or genetic markers of insulin-dependent diabetes mellitus and thus do not appear to be at an increased risk for development of insulin-dependent diabetes mellitus. Our data suggest that insulin autoantibodies develop in children subject to sickle cell crises.

Acute Disease↗

PubMed2006

Japanese IGT subjects with high insulin response are far more frequently associated with the metabolic syndrome than those with low insulin response.

Impaired glucose tolerance (IGT) represents a prediabetic state positioned somewhere between normal glucose tolerance and diabetes, which is also assumed to make individuals in this state highly susceptible to atherosclerotic disease. IGT also accounts for a highly heterogeneous population, with the condition varying from individual to individual. In this study, we stratified subjects with IGT by their insulin response and compare the pathology of IGT when it is associated with high or low insulin response to gain insight into the diverse pathology of IGT. Of the male corporate employees who underwent 75 g OGTT at the corporation's healthcare center, 150 individuals diagnosed with IGT (isolated IGT, combined IGT and IFG) comprised our study subjects. The study subjects were stratified into four quartiles by percentile AUC for insulin, and those in the 25th or less percentile were defined as the low insulin response group (n = 37), vs those in the 76th or greater percentile defined as the high insulin response group (n = 38), and these groups were compared. There was no significant difference observed between the two groups in regard to post-OGTT glucose response and area under the glucose curve. However, the high insulin response group was associated with higher BMI, subcutanesous fat area, uric acid levels, HOMA-beta cell values, and delta insulin/delta glucose (30 min) than the low insulin response group. The number of risk factors for the metabolic syndrome detected (as defined by the ATPIII diagnostic criteria) per subject was 2.84 +/- 0.17 and 2.08 +/- 0.20, respectively, in the high insulin response group and in the low insulin response group, with the number significantly (p < 0.05) higher in the high insulin response group. Furthermore, the incidence of the metabolic syndrome as defined by the ATPIII diagnostic criteria was 63.2% (24/38) in the high insulin response group vs 32.4% (12/27) in the low insulin response group, with the incidence significantly (p < 0.01) higher in the high insulin response group. Likewise, the incidence of the metabolic syndrome as defined by the Japanese diagnostic criteria was found to be significantly (p < 0.05) higher in the high insulin response group at 50% (19/38) compared to 27.0% (10/37) in the low insulin response group. Our study findings suggest that IGT subjects with high insulin response and those with low insulin response vary greatly in regard to the number of atherosclerotic risk factors complicated and the frequency with which they are associated with the metabolic syndrome. It is also shown in middle-aged Japanese males that of the two forms of IGT, IGT with high insulin response is more closely linked to the pathogenesis of atherosclerotic cardiovascular disease.

Atherosclerosis↗

PubMed1997

Exercise training in Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus: effects on the B-cell mass, insulin content and fibrosis in the pancreas.

The effects of exercise on alterations in the amount of B-cell mass, insulin content and fibrous tissue present in the pancreas were examined for a diabetic state induced by a 70% pancreatectomy and a prediabetic state in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model for the spontaneous development of non-insulin-dependent diabetes mellitus (NIDDM). The rats (5-weeks old) were trained either by a 6-week running program or sedentary controls, and at 6-weeks of age, received either a 70% pancreatectomy or a sham-pancreatectomy (sham). As in our previous report, persistent hyperglycemia was detected after surgery for both trained pancreatectomized (Px) and sedentary Px groups. In the nondiabetic sham rats, exercise training resulted in a significantly smaller increase in body weight and beneficial effects on the pancreas as reflected by an increase in pancreatic volume, accompanied by increases in B-cell mass and insulin content as well as less connective tissue in the pancreas compared with the sedentary nondiabetic sham rats. The effect was not sufficient to improve sustained hyperglycemia in the trained diabetic Px rats. This is probably due to a decreased capacity for B-cell proliferation in response to an increased demand for insulin. Although exercise failed to improve this inherent defect in B-cell proliferation, it ameliorated the further deterioration of the pancreas which occurred with hyperglycemia, and resulted in a higher quantity of insulin stored per milligram of B-cell mass (as function of B-cell mass) and less fibrosis in the pancreas, compared with the sedentary diabetic Px rats. The findings of the present study suggest that exercise training has a beneficial effect on the pancreas in the nondiabetic state, and also exerts some positive effects in the diabetic state in this model rat.

Animals↗

PubMed2000

Insulin secretion and insulin sensitivity in diabetic subgroups: studies in the prediabetic and diabetic state.

AIMS/HYPOTHESIS: To evaluate insulin sensitivity and insulin secretion in prediabetic and diabetic subjects with mutations in MODY1 (HNF-4 alpha) and MODY3 (HNF-1 alpha) genes, in subjects with GAD antibodies, latent autoimmune diabetes in adults and in subjects with the common form of Type II (non-insulin-dependent) diabetes mellitus. METHODS: Insulin secretion was measured as the incremental 30-min insulin (I30) and insulin glucose ratio (I:G30) during OGTT whereas insulin sensitivity was measured as the insulin sensitivity index during OGTT in 131 carriers of MODY mutations [NGT = 38, IFG/IGT = 21, diabetes mellitus (DM) = 72], in 293 subjects with GADA (NGT = 47, IFG/IGT = 29, DM = 217) and in 2961 subjects with a family history of the common form of Type II diabetes but without MODY mutations or GADA (NGT = 1360, IFG/IGT = 857, DM = 744). A subgroup of the subjects underwent a euglycaemic clamp (n = 210) and intravenous glucose tolerance test (n = 337) for the estimation of insulin sensitivity and first-phase insulin secretion. RESULTS: Non-diabetic subjects with MODY mutations had pronounced impaired insulin secretion (I30, I:G30) compared with the two other groups (p = 0.005). Normal or non-diabetic glucose tolerance was maintained by enhanced insulin sensitivity compared with the other two groups (p < 0.05 and p < 0.005). In contrast to patients with Type II diabetes and with adult latent autoimmune diabetes, MODY patients showed only a modest deterioration in insulin sensitivity at onset of diabetes. The 2-h glucose values inversely correlated with insulin sensitivity in subjects with GADA (r = -0.447, p < 0.001) and subjects from Type II diabetic families (r = -0.426, p < 0.001), whereas no such relation was observed in subjects with MODY mutations (r = 0.151, p = NS). There were no statistically significant differences in insulin secretion or insulin sensitivity between subjects with GADA or subjects with a family history of Type II diabetes, either at the NGT or the IFG/IGT stage. CONCLUSION/INTERPRETATION: Glucose-tolerant carriers of MODY mutations are characterised by a severe impairment in insulin secretion. Enhanced insulin sensitivity is the most likely explanation for the normal glucose tolerance. Whereas subjects with positive GADA or Type II diabetes have impaired insulin sensitivity with increasing glucose concentrations, MODY mutation carriers seem to be protected from the effect of glucose toxicity.

Adult↗

PubMed1993

Peripheral insulin resistance precedes the onset of hyperglycemia in spontaneously diabetic Chinese hamsters of Asahikawa colony.

To investigate the pathogenesis of spontaneously diabetic Chinese hamsters of Asahikawa colony (CHAD), hepatic glucose production (HGP) and glucose uptake of several tissues were determined before the onset of hyperglycemia (prediabetic state). HGP was calculated as glucose disposal in postabsorptive state using [3-3H]glucose. Glucose uptake of various tissues was assessed as glucose utilization index (R'g) by the 2-deoxyglucose method. Plasma insulin level was increased in prediabetic CHAD but not decreased in CHAD with short-term diabetes compared with control Chinese hamsters (non-diabetic strain). HGP of prediabetic CHAD was similar to that of control Chinese hamsters. However, after developing overt hyperglycemia (> 200 mg/100 ml), HGP increased linearly with plasma glucose level. R'g of adductor longus, extensor digitorum longus and triceps was significantly decreased in prediabetic CHAD. R'g of interscapular brown adipose tissue, white adipose tissue from inguinal, dorsal and epididymal sites were also decreased in prediabetic CHAD. Thus, peripheral insulin resistance precedes the development of hyperglycemia and may be a primary defect in CHAD. No significant difference of R'g in heart ventricle, diaphragm, tibialis anterior or brain was observed. In conclusion, insulin resistance in some muscles and brown and white adipose tissues precedes hyperglycemia and hepatic insulin resistance in CHAD. Hepatic overproduction of glucose (hepatic insulin resistance) is a major factor responsible for overt basal hyperglycemia and may play an important role in developing further diabetic state.

Adipose Tissue↗

PubMed1985

"Activated" T-lymphocyte levels in the spontaneously diabetic BB rat syndrome.

About 50% of individual members of a diabetes-prone stock of BB rats eventually become hyperglycemic (usually between 60 and 180 days of age) while the remainder remain normoglycemic for life. Circulating levels of Ia antigen bearing T-lymphocytes from different lymphoid compartments of acutely diabetic and normoglycemic (but diabetes prone) BB rats were determined with monoclonal antibodies in an effort to analyze the temporal relationship between levels of this unusual T cell antigen and the onset of diabetes. In young normoglycemic rats elevated blood levels of Ia-positive T-lymphocytes (greater than or equal to 4.00%) predicted the future development of hyperglycemia with a sensitivity of 85% and a specificity of 83%. The interval between the identification of these elevated levels and the onset of diabetes ranged from 22 to 82 days. After the development of hyperglycemia the level of Ia-positive T-lymphocytes declined progressively in all lymphoid compartments with chronicity of the diabetes. We conclude that Ia antigens bearing T cells serve as immunologic "markers" of susceptibility to diabetes in this "high-risk" population and probably reflect an ongoing immune process during the prediabetic state. Similar findings in humans with a family history of diabetes might lead to identification of prediabetic individuals and allow selective use of immunomodulation to prevent the disease.

Acute Disease↗

PubMed1997

Pronounced insulin resistance and inadequate beta-cell secretion characterize lean gestational diabetes during and after pregnancy.

OBJECTIVE: To evaluate beta-cell secretion and glucose metabolism in lean subjects with gestational diabetes mellitus (GDM) compared with that in subjects with normal pregnancy and obesity. RESEARCH DESIGN AND METHODS: Insulin secretion, insulin sensitivity (S1), and hepatic insulin extraction were assessed in pregnant women with GDM before and after delivery and in those with normal glucose tolerance (NGT) in comparison to healthy nonpregnant lean and obese women. Kinetic analysis of glucose, insulin, and C-peptide plasma concentrations during oral and intravenous glucose tolerance tests was performed by mathematical modeling. RESULTS: S1 was blunted in pregnant women with GDM by 84% and in those with NGT by 66% compared with lean nonpregnant women (P < 0.005 vs. healthy nonpregnant lean control subjects; P < 0.05, GDM vs. pregnant women with NGT), whereas glucose effectiveness was decreased by 33% in both pregnant groups (P < 0.05 vs. healthy nonpregnant lean control subjects). Insulin secretion was 30% higher (P < 0.05) in subjects with GDM than in pregnant women with NGT or in nonpregnant lean women, but decreased (P < 0.005) when compared with obese women with a comparable degree of insulin resistance. Fractional hepatic insulin extraction was similar in both pregnant groups, being lower (P < 0.0001) by 30% versus nonpregnant females. beta-cell sensitivity to glucose for insulin release was decreased in subjects with GDM versus pregnant women with NGT as well as nonpregnant women by 40-50% (P < 0.01). Twelve weeks after delivery, GDM returned to normal glucose tolerance, but S1 remained 50% lower than that in lean nonpregnant women, while beta-cell sensitivity to glucose did not change (P < 0.01 vs. healthy nonpregnant lean control subjects). CONCLUSIONS: Pregnancy is characterized by insulin resistance, diminished hepatic insulin extraction, and glucose effectiveness. Lean subjects with GDM are additionally characterized by having more pronounced insulin resistance and inadequate insulin secretion, which persist after delivery. Compared with other insulin-resistant prediabetic states like impaired glucose tolerance (IGT), defective insulin secretion seems to be a predominant defect in lean GDM subjects, indicating that it might represent a specific prediabetic condition.

Adult↗

PubMed2000

Islet autoantibodies as potential markers for disease recurrence in clinical islet transplantation.

At present, indications for clinical islet transplantation exist almost exclusively in type-1 diabetic patients with end-stage renal disease receiving the islets either simultaneously with or after an already established kidney graft. This implies, that islet transplantation is performed in type-1 diabetic patients with long disease duration. The fate of the islet allograft is determined by a combination of immunological effector mechanisms. Beside early non-specific inflammation and alloreactivity, chronic autoimmunity may contribute to islet graft failure. The immunologic characterization of the prediabetic state has considerably progressed, whereas, the nature of autoimmunity years and decades after the onset of diabetes is largely unknown. Islet autoantibodies as surrogate markers for islet autoimmunity are well established in prediabetic periods of type-1 diabetes. In contrast, only few data exists in the setting of long-term type-1 diabetic patients undergoing islet transplantation. This article reviews the original data from the Giessen islet transplantation project and the pertinent literature with respect to islet autoimmunity and disease recurrence. It is demonstrated, that autoimmunity may persist in an individual with type-1 diabetes for decades after diabetes onset and that autoimmune responses to transplanted islets are resistant to the immunosuppressive drugs currently used. It is suggested from pilot trials, that type-1 diabetic patients with persistent autoantibodies and individuals, in whom autoantibodies become detectable after the transplantation are at higher risk for early islet graft failure potentially due to recurrent autoreactivity directed to the islet graft.

Autoantibodies↗

PubMed2004

Effects of micronized fenofibrate on insulin resistance in patients with metabolic syndrome.

BACKGROUND AND OBJECTIVE: Metabolic syndrome is characterized by insulin resistance (IR) as well as dyslipidemia, ventral overweight, hypertension and elevated fasting plasma glucose. Since diabetic and prediabetic states are commonly associated with hypertriglyceridemia, fenofibrates have been used in such patients. The aim of this pilot open trial was to study the influence of micronized fenofibrate on insulin resistance and plasma insulin levels in prediabetic and diabetic patients. SUBJECTS: From 114 dyslipidemic patients, 31 with dyslipidemia and insulin resistance were selected to take part in the study. Of the 31 patients, 20 were nondiabetic and only 11 had noninsulin-dependent diabetes mellitus. Eighteen dyslipidemic patients acted as controls. METHODS: Insulin resistance was assessed in a short-term insulin tolerance test. Plasma insulin, antiinsulin antibodies, lipid parameters and the insulin sensitivity index (ISI) were measured at entry and after a 3-month therapy with 200 mg micronized fenofibrate daily. RESULTS: Three-month therapy with micronized fenofibrate resulted in significant ISI increase and was accompanied by a decrease in plasma insulin levels in dyslipidemic patients with metabolic syndrome. ISI also improved in patients with type 2 diabetes mellitus and there was an unexpected increase in plasma insulin levels. Antiinsulin antibodies were unchanged throughout the trial. Reductions in plasma triglycerides and total cholesterol exceeding 50% and 20%, respectively, were observed in patients with metabolic syndrome. These changes were accompanied by an increase in mean levels of plasma high-density lipoprotein (HDL) cholesterol (above 35%). CONCLUSIONS: Micronized fenofibrate is an effective drug in normalizing lipid-lipoprotein levels in patients with metabolic syndrome. After a 3-month fenofibrate therapy, insulin resistance was reduced in a group of patients with dyslipidemia and metabolic syndrome.

Diabetes Mellitus, Type 2↗