BACKGROUNDType 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions. However, the evaluation of beta cell functions is either expensive or inconvenient for clinical practice. We aimed to elucidate the association between the changes of insulin responsiveness and the fasting plasma glucose (FPG) during the development of diabetes.

METHODSA total of 1192 Chinese individuals with normal blood glucose or hyperglycemia were enrolled for the analysis. The early insulinogenic index (DeltaI30/DeltaG30), the area under the curve of insulin (AUC-I), and homeostasis model assessment were applied to evaluate the early phase secretion, total insulin secretion, and insulin resistance respectively. Polynomial regression analysis was performed to estimate the fluctuation of beta cell functions.

RESULTSThe DeltaI30/DeltaG30 decreased much more rapidly than the AUC-I accompanying with the elevation of FPG. At the FPG of 110 mg/dl (a pre-diabetic stage), the DeltaI30/DeltaG30 lost 50% of its maximum while the AUC-I was still at a compensated normal level. The AUC-I exhibited abnormal and decreased gradually at the FPG of from 130 mg/dl to higher (overt diabetes), while the DeltaI30/DeltaG30 almost remained at 25% of its maximum value. When hyperglycemia continuously existed at > 180 mg/dl, both the DeltaI30/DeltaG30 and AUC-I were totally lost.

CONCLUSIONThe increased fasting plasma glucose reflects progressive decompensation of beta cell functions, and could be used to guide the strategy of clinical treatments.

Adult ; Aged ; Aged, 80 and over ; Blood Glucose ; analysis ; Diabetes Mellitus ; blood ; physiopathology ; Fasting ; blood ; Female ; Humans ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; physiology ; Male ; Middle Aged

This paper reported a case of congenital hyperinsulinism and reviewed the relevant literatures regarding to the etiology, pathogenesis, clinical and pathological features, diagnosis and treatment of this disorder. The baby (male), with gestational age of 36 weeks and birth weight 4,200 g, was delivered by caesarean section. It presented with hypoglycemia immediately after birth (0.8 mmol/L). Through the course of the disease, the baby's blood sugar manifested with 1.2-2.8 mmol/L although glucocorticoid was administered. 10% glucose solutions were intravenously infused at a speed of 10-17 mg/(kg x min) for this patient to retain a stable blood sugar level. The plasma insulin level was 24.13 U/L and blood sugar level was 1.5 mmol/L on day 30 of his life. The ratio of plasma insulin (U/L) and plasma glucose (mg/dL) was 0.89. These results suggest an inappropriate insulin secretion resulting in persistent hypoglycemia in this baby and so it was definitely diagnosed with congenital hyperinsulinism.
Blood Glucose ; analysis ; Diagnosis, Differential ; Humans ; Hyperinsulinism ; congenital ; diagnosis ; therapy ; Infant, Newborn ; Insulin ; secretion ; Male ; Prognosis

OBJECTIVETo analyze the changes of patients with type 2 diabetes in different stages in glucagon (GC) and free fatty acid (FFA) in fasting, OGT and L-Arg experiments, and discusses the role of pancreatic alphabeta cells in diabetes pathogenesis by studying the relations among indexes such as glucagon (GC), free fatty acid (FFA) and blood glucose (BG), insulin, insulin homeostasis model (HOMA) and glucose metabolism hormone secretion curve, in order to provide theoretical basis for the treatment of diabetes.

METHODStudy objects were divided into the T2DM group (45 cases), the IGT group (28 cases) and the NGT group (30 cases) for an OGTT experiment and then an L-Arg experiment on the next day. Under the fasting state, their blood glucose (FBG), insulin (F), glucagon (FGC), free fatty acid (FFA) were detected to calculate HOMA-beta, insulin sensitivity index (ISI) and HOMA-IR of different groups. Meanwhile, efforts were made to calculate different time quantum detected in OGTT and L-Arg experiments and area under the curve AUC(BG), AUC(INS) and AUC(GC).

RESULTObvious overall differences were observed in FFA and FGC of the three groups. FGC of each group was negatively correlated with HOMA-beta and ISI. Among all of the 103 study objects, FGC was positively correlated with FBG and HOMA-IR and negatively correlated with HOMA-beta and ISI, with no correlation with FINS; FFA was positively correlated with FBG, HOMA-IR and negatively correlated with FINS, HOMA-beta, ISI. FGC and FFA were positively correlated in the T2DM group and the IGT group, but with no statistical correlation in the NGT group. The sequence of the three study objects was T2DM > IGR > NGT in AUC(GC) in the OGTT experiment and T2DM > IGR > NGT in in AUC(GC) in the L-Arg experiment, with the significant positive correlation between AUC(GC) and AUC(BG) and significant negative correlation with AUC(INS).

CONCLUSIONGlucagon and free fatty acid of T2DM and IGT patients increased, which was positively correlated with blood glucose and HOMA-IR and negatively correlated with INS, HOMA-beta and ISI. The increase in glucagons of T2DM and IGT patients indicated inappropriate secretion of pancreatic alphabeta cells among patients with type 2 diabetes.

Adult ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; Fatty Acids, Nonesterified ; metabolism ; Female ; Glucagon ; blood ; Humans ; Insulin ; secretion ; Islets of Langerhans ; secretion ; Male ; Middle Aged

OBJECTIVETo investigate the secretion patterns of glucose-dependent insulinotropic polypeptide (GIP) after different dietary loads in subjects with normal glucose tolerance (NGT) and their relation to insulin secretion and plasma glucose levels.

METHODSFourteen subjects with normal glucose tolerance underwent 75 g glucose tolerance test(OGTT) followed by mixed meal tolerance test(MMT) one week later. Blood glucose, insulin, and GIP were measured in the fasting state and at 0, 15, 30, 60, 90 and 120 min after glucose load or mixed meal load.

RESULTSThe first peak value of GIP after glucose load occurred at 15 min (45.09∓4.67 pmol/L). After a brief decline, GIP continued to increase till reaching 59.66∓11.73 pmol/L at 120 min after the load. After the mixed meal load, GIP secretion presented with two peaks: the first peak appeared at 15 min (71.69∓14.19 pmol/L) with a level significantly higher than that at 15 min following glucose load (P<0.05), and the second occurred at 90 min (55.35∓13.19 pmol/L). The area under curve of GIP showed no significant difference between the two loads (P>0.05). Compared with glucose load, mixed meal load resulted in an increase of the first GIP peak and an earlier insulin peak (30 min vs 60 min), but a significant decrease of blood glucose at 15 min (P<0.05).

CONCLUSIONCompared with glucose load, mixed meal (containing fat) can strongly stimulate GIP release and cause earlier occurrence of the insulin peak, which might be an important reason for the lower blood glucose after mixed meal.

Adult ; Blood Glucose ; metabolism ; China ; ethnology ; Diet ; Energy Intake ; Female ; Gastric Inhibitory Polypeptide ; secretion ; Glucose Tolerance Test ; Humans ; Insulin ; secretion ; Male ; Middle Aged ; Young Adult

This animal experiment was aimed at the questions whether high glucose concentration inhibits insulin secretion (glucose toxicity, GT) of beta-cell of islets from SHR and Wistar-Kyoto (WKY) rat and whether adrenomedullin (AM) enhances GT. Ten 6-week-old SHRs (test group) and ten 10-week-old Wistar-Kyoto rats (WKY) (control group) were selected. RAMI-1640 medium containing 5.6 mM glucose (normal glucose group) and 20 mM glucose (high glucose group) were applied. Various concentrations of AM (0, 10(-8), 10(-7), 10(-6) M) and RPMI-1640 medium containing high glucose were mixed, respectively. The isolated islets from rats were put into 12-well plates (90 islets/well). The islets were incubated in RAMI-1640 medium containing normal or high glucose for one hour. Then the supernatants from both incubations were determined by RIA for insulin. In SHR group, the insulin concentration in supernatants gained from high glucose group without AM was lower than that from normal glucose group (19.9+/-6.6 vs 60.9+/-33.6 mU/L, P<0.05). With the increment of the concentration of AM, insulin concentration in supernatants from islets incubated in high glucose and various concentrations of AM tended to be low further (19.9+/-6.6 vs 22.2+/-8.0 vs 21.5+/-5.6 vs 17.9+/-3.6 mU/L). The changing tendency in control group was the same as in SHR group. When the islets were incubated in normal glucose and high glucose medium, the insulin concentration in supernatant significantly decreased in SHR group compared with that in control group (P<0.01). The insulin secretion was inhibited by high glucose in beta-cell of islets from SHR and WKY. The results suggest GT to beta-cell of islets from SHR and WKY. AM tended to inhibit insulin secretion in a dose-dependent manner in beta-cell of islets from SHR and WKY. The inhibition of insulin secretion caused by high glucose in beta-cell of islets from SHR was more remarkable than from WKY. This may be related to secretion dysfunction in beta-cell of islets from SHR.
Adrenomedullin ; Animals ; Blood Glucose ; metabolism ; Cells, Cultured ; Female ; Glucose ; pharmacology ; Hyperglycemia ; blood ; Hypertension ; metabolism ; pathology ; Insulin ; secretion ; Insulin Resistance ; Islets of Langerhans ; drug effects ; pathology ; secretion ; Male ; Peptides ; pharmacology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

BACKGROUNDThis prospective, randomized, controlled study was designed to investigate the effects of a diabetes specific formula (Diason low energy: 313.8 kJ/100 ml), compared with a standard formula, on insulin sensitivity, serum C peptide, serum lipids and free fatty acid (FFA) in type 2 diabetics.

METHODSIn total of 71 type 2 diabetics completed the study. Enteral formulas were given orally as the sole source of nutrition to the subjects for 6 days. Venous blood samples (0.5, 1, 2, 3 hours) were collected at day-7 after a 75 g oral glucose tolerance test (OGTT), day 1 after a standard test meal (1673.6 kJ) and after 6 days of either the test diabetes specific formula or a standard formula. Plasma glucose, serum insulin, C peptide and lipids were measured.

RESULTSAfter the intervention period, the diabetes specific formula resulted in a significantly lower postprandial rise in blood glucose concentrations at 0.5 hour (P < 0.05) and 1 hour (P < 0.01); significantly lower peak height of plasma glucose (P = 0.05); significantly lower plasma insulin concentrations at 0.5 hour (P < 0.01), 1 hour (P < 0.01) and 2 hours (P < 0.01); and a significantly lower plasma insulin peak compared to controls; both OGTT and a standard test meal (P < 0.05). The glucose and insulin area under the curve after the diabetes specific formula compared to the standard formula were significantly lower. The C peptide level was lower after 6 days of both nutrition formulas compare to 75 g OGTT, but not different from the standard mixed meal. Both formulas were well tolerated.

CONCLUSIONSIn summary the diabetes specific formula with a relatively high monounsaturated fatty acid and high multi fiber proportion significantly improved glycemic control. On top of this, the insulin sensitivity (HOMA-IS) was significantly improved and may therefore directly improve the impact on long term complications. The disease specific formula should therefore be the preferred option to be used by diabetic and hyperglycemic patients in need of nutritional support.

C-Peptide ; blood ; Diabetes Mellitus, Type 2 ; blood ; diet therapy ; Diet, Diabetic ; Fatty Acids, Nonesterified ; blood ; Humans ; Insulin ; secretion ; Lipids ; blood ; Middle Aged ; Prospective Studies

The purpose of the present study is to investigate the effects of urotensin II (UII) on insulin secretion in islet beta cells and the underlying mechanism. Glucose tolerance test was performed in Wistar rats to evaluate the effect of UII on the levels of plasma glucose and insulin. Static incubation experiment was employed to investigate the effect of UII on glucose-induced insulin secretion (GIIS) in betaTC-6 cells. After the incubation, insulin content and mRNA level in betaTC-6 cells were analyzed. Finally, Western blot was used to find out if UII could change the expression levels of pancreatic duodenal homeobox-1 (PDX-1) and glucokinase (GCK). It was observed that intravenous administration of UII (30, 300 nmol/kg) resulted in a significant decrease in insulin level 15 min after glucose load, and induced an obvious increase in plasma glucose 90 min after the load. In vitro, two hours of UII incubation inhibited GIIS in betaTC-6 cells without affecting insulin content and mRNA levels. The inhibitory effect of UII was blocked by UII receptor antagonist (urantide), and partially blunted by protein kinase C (PKC) inhibitor (chelerythrine) and somatostatin receptor antagonist (cyclosomatostatin). Moreover, we found that GCK protein level was significantly reduced by UII, while PDX-1, a key regulator of insulin gene transcription in beta cells, was not affected. These results suggest that UII-induced inhibition of GIIS in betaTC-6 cells are mediated by UII receptor and PKC pathway, as well as somatostatin receptor which could be activated by high dose of UII. The inhibitory effect of UII on insulin secretion is rather associated with a suppression of GCK expression than a regulation on PDX-1 expression.
Animals ; Blood Glucose ; metabolism ; Cell Line ; Glucokinase ; metabolism ; Homeodomain Proteins ; metabolism ; Insulin ; secretion ; Insulin-Secreting Cells ; metabolism ; physiology ; secretion ; Male ; Mice ; Rats ; Rats, Wistar ; Trans-Activators ; metabolism ; Urotensins ; pharmacology

This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve beta-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients.
Adipokines/blood ; Animals ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy ; Dietary Supplements ; Dyslipidemias/blood/*drug therapy ; Glucose Tolerance Test ; Hyperglycemia/blood/*drug therapy ; Hypoglycemic Agents/administration & dosage/*pharmacology ; Hypolipidemic Agents/administration & dosage/*pharmacology ; Insulin/physiology/secretion ; Insulin Resistance ; Insulin-Secreting Cells/physiology/secretion ; Leptin/*blood ; Lipid Metabolism/drug effects ; Lipids/blood ; Male ; Organ Specificity ; Rats ; Rats, Long-Evans ; Taurine/administration & dosage/*pharmacology

OBJECTIVETo discuss the potential application of artificial neural network (ANN) on the epidemiological classification of disease.

METHODSLearning vector quantification neural network (LVQNN) and discriminate analysis were applied to data from epidemiological survey in a mine in 1996.

RESULTSThe structure of LVQNN was 25-->13-->3. The total veracity rates was 96.98%, and 92.45% among the abnormal blood glucose individuals. Through stepwise discriminate analysis, the discriminate equations were established including 11 variables with a total veracity rate of 87.34%, but was 85.53% in the abnormal blood glucose individuals. Further analysis on 30 cases with missing values showed that the disagreement ratio of LVQ was 1/30, lower than that of discriminate analysis of 7/30.

CONCLUSIONSCompared to the conventional statistics method, LVQ not only showed better prediction precision, but could treat data with missing values satisfactorily plus it had no limit to the type or distribution of relevant data, thus provided a new powerful method to epidemiologic prediction.

Algorithms ; Blood Glucose ; metabolism ; China ; epidemiology ; Diabetes Mellitus ; blood ; classification ; epidemiology ; Glucose Tolerance Test ; Humans ; Insulin ; blood ; secretion ; Logistic Models ; Neural Networks (Computer)

This investigation was made in regard to the changes of plasma Leptin, Tumor Necrosis Factor-alpha (TNF-alpha) and Neuropeptide Y (NPY) levels and their association with insulin resistance and beta-cell secretion function in normal glucose tolerant first-degree relatives of familial type 2 diabetic pedigrees in Chengdu area. Levels of Leptin, TNF-alpha, NPY and lipids (TG, TC, HDL-C) were determined in 86 type 2 diabetic mellitus (DM) patients, 73 normal glucose tolerant (NGT) first-degree relatives in familial type 2 diabetic pedigrees and 65 normal controls (NC) from non-diabetic families. All of the subjects underwent 75 g oral glucose tolerance test (OGTT). Plasma glucose, immunoreactive insulin (IRI) and true insulin (TI) levels were also determined. Fasting glucose and TI levels were used to calculate homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-beta cell indexes. After being adjusted for age and body mass index (BMI), the levels of Leptin in DM and NGT first-degree relatives were all significantly higher than that in normal controls (P < 0.05). Type 2 diabetic patients showed significantly elevated TNF-alpha levels than did the normal controls (P < 0.05). Furthermore, diabetic subjects showed significantly higher HOMA-IR and lower HOMA-B levels, compared with those in NGT and NC groups (P < 0.05). No statistically significant difference was found in regard to NPY among three groups. NGT first-degree relatives showed significantly higher levels of TG, fasting IRI, OGTT-2h IRI and HOMA-IR than did the normal controls (P < 0.05). Leptin was positively correlated with age, BMI, waist, A1c, fasting and OGTT-2h glucose, OGTT-2h TI and TNF-alpha in all subjects, and was negatively correlated with HOMA-B in females. Leptin levels were significantly elevated in NGT first-degree relatives, which implied that genetic defects of Leptin may play a role in the development of familial type 2 diabetic pedigrees.
Adult ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; genetics ; Female ; Glucose Tolerance Test ; Humans ; Insulin ; secretion ; Insulin Resistance ; Leptin ; blood ; Male ; Middle Aged ; Neuropeptide Y ; blood ; Pedigree ; Tumor Necrosis Factor-alpha ; blood