OBJECTIVETo evaluate the effect of short-term intensive therapy on blood glucose control, BETA-cell function, and blood lipid levels in newly diagnosed type 2 diabetic patients.

METHODSOut-patients with newly diagnosed type 2 diabetic patients were enrolled for intensive treatment with sulfonylureas and metformin for 12 weeks, and the therapeutic effect was evaluated.

RESULTSAfter the intensive treatment, FPG, 2 hPG, and HbA1c decreased significantly (P<0.01); HOMA-IR decreased and HOMA-B increased significantly (P<0.01), and TG, CHOL, LDL decreased significantly (P<0.01) after the treatment.

CONCLUSIONShort-term intensive treatment with glimepiride combined with metformin is safe and effective in newly diagnosed type 2 diabetic patients with HbA1c>9%.

Diabetes Mellitus, Type 2 ; drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Male ; Metformin ; therapeutic use ; Sulfonylurea Compounds ; therapeutic use ; Treatment Outcome

Adolescent ; Diabetes Mellitus ; drug therapy ; metabolism ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Infant, Newborn ; Male ; Sulfonylurea Compounds ; adverse effects ; therapeutic use

Insulin resistance is frequently associated with chronic liver disease, and the interaction between hepatitis C virus (HCV) infection and insulin resistance is a major public health issue, bound to increase in the near term. Because of their potential synergism on liver disease severity, a better understanding of the clinical consequences of the relationship between HCV infection and insulin resistance is needed. This translates into accelerated liver disease progression, reduced response to anti-viral agents and, in susceptible individuals, increased risk of developing type 2 diabetes. HCV may also cause hepatic steatosis, especially in patients infected with genotype 3, although the clinical impact of viral steatosis is debated. Little is known regarding the effect of anti-diabetic agents on HCV infection, and a possible association between use of exogenous insulin or a sulfonylurea agents and the development of hepatocellular carcinoma has recently been reported. Thus, modified lifestyle and pharmacological modalities are urgently warranted in chronic hepatitis C with metabolic alterations.
Antiviral Agents/therapeutic use ; Diabetes Mellitus, Type 2/complications/drug therapy/metabolism ; Genotype ; Hepatitis C, Chronic/*drug therapy/etiology/metabolism ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin/therapeutic use ; *Insulin Resistance ; Liver Cirrhosis/etiology ; Liver Neoplasms/etiology ; Sulfonylurea Compounds/therapeutic use

The alterations in atherogenic index of plasma (AlP) in type 2 diabetic patients and their normoglycemic first-degree relatives (NFDR) were investigated, and the effects of Acarbose or Glimepiride on AIP in 99 type 2 diabetic patients were evaluated. Triglycerride (TG), total cholesterol, high density lipoprotein-cholesterol (HDL-C) levels were analyzed, and Log (TG/HDL-C) was calculated as AIP in 62 type 2 diabetic patients and their 67 NFDR from 29 type 2 diabetic pedigrees and in 45 healthy controls without family histories of diabetes. Also analyzed were the same parameters in 99 type 2 diabetic patients before and after therapy with Acarbose or Glimepiride. The results revealed that diabetic patients and their NFDR had significantly higher AIP than did the controls, whereas no significant differences were seen between diabetic patients and their NFDR. Positive correlation of AIP between type 2 diabetic patients and their offspring were observed (r = 0.241, P < 0.05). After 8 weeks therapy with Acarbose, the AIP of type 2 diabetic patients was decreased significantly, and no differences were observed for AIP levels in Glimepiride group although the AIP was lower when compared with the untreated level. As a significant inverse correlation of small dense low density lipoprotein (sdLDL) with AIP was confirmed, our data suggest that diabetic patients and their NFDR from type 2 diabetic pedigrees had significantly higher AIP than did controls; AIP could be decreased by therapy with Acarbose in type 2 diabetic patients; Glimepiride may bring potential benefit to type 2 diabetic patients by influencing sdLDL.
Acarbose ; therapeutic use ; Atherosclerosis ; blood ; Body Mass Index ; Case-Control Studies ; Cholesterol, HDL ; blood ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Humans ; Hypoglycemic Agents ; therapeutic use ; Pedigree ; Sulfonylurea Compounds ; therapeutic use ; Triglycerides ; blood

BACKGROUNDDiabetic cardiovascular complication is a major cause of mortality in type 2 diabetic patients. Hyperglycemia markedly increases the risk of cardiovascular disease. Endothelial dysfunction is common in type 2 diabetes mellitus (DM) and is an early indicator of diabetic vascular disease. Therefore, it is necessary to identify the effect of different hypoglycemic agents on vascular endothelium. The aim of the study was to examine and compare the effects of metformin and gliquidone on atherosclerotic lesions in streptozotocin-induced diabetic rats.

METHODSForty male Sprague-Dawley rats (age, 8 weeks; weight, 180-200 g) were included in this study and fed with a normal chow diet for 1 week. Rats (n = 10) served as the normal control group (NC group) were fed with a normal chow for another 2 weeks and received an injection of saline. The rest 30 rats fed with a high-fat diet for 2 weeks and injected streptozotocin were randomly assigned to three groups (n = 10 rats per group) as follow: type 2 DM group (DM group), DM + gliquidone group (GLI group) and DM + metformin group (MET group). Five weeks later, all rats were fasted overnight and taken tail blood samples for biochemical determinations. Then rats in the NC and DM groups were administrated with normal saline, while rats in the MET and GLI groups were administrated with metformin (100 mg/kg) or gliquidone (10 mg/kg), respectively. All medicines were given via intragastric administration for 8 weeks. After 16 weeks, plasma triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) were measured. The aortic arch was isolated from diabetic rats and was assessed by pathological sectioning using H&E staining.

RESULTSMetformin treatment prevented weight gain ((315.80 ± 52.16) g vs. (318.70 ± 68.48) g, P = 0.773), improved plasma TG, HDL-C and LDL-C levels (P = 0.006, 0.003, 0.001, respectively, all P < 0.05). However, gliquidone showed no significant effects on plasma TG and TC levels (P = 0.819, 0.053, respectively). LDL-C and HDL-C in the GLI group changed ((0.46 ± 0.10) mmol/L vs. (0.36 ± 0.14) mmol/L, P = 0.007; (0.99 ± 0.27) mmol/L vs. (1.11 ± 0.18) mmol/L, P = 0.049). Both metformin and gliquidone treatment lowered blood glucose levels (P = 0.001, 0.004, respectively, P < 0.05). Under light microscopy, no changes were observed in the aortic wall structure of each layer; the intima was smooth and the membrane elastic fibers were normal in the NC group. In the DM group, the aortic wall structure was unclear, the intima was thickened with irregular intima, and membrane elastic fibers collapsed. The aortic intima in the MET and GLI groups was smoother compared with the DM group, but the endothelial structure of the MET group was closer to that of the NC group.

CONCLUSIONSBoth metformin and gliquidone have anti-atherosclerotic effects. But the endothelial structure of the MET group was closer to that of the NC group. Metformin and gliquidone therapy can reduce serum level of LDL-C and increase level of HDL-C, whereas gliquidone therapy did not lose weight and decrease serum level of TG. These data may have important implications for the treatment of patients with type 2 DM.

Animals ; Aorta ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Angiopathies ; prevention & control ; Hypoglycemic Agents ; therapeutic use ; Male ; Metformin ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sulfonylurea Compounds ; therapeutic use

OBJECTIVE: To explore the variations of early-phase insulin secretion in Type 2 diabetic patients in different stages. METHODS: L-arginine stimulative test, fast blood glucose and body mass index (BMI) were evaluated in 40 nomal controls (NC) and 101 Type 2 diabetic patients. The diabetic patients were divided into three groups: newly diagnosed group (n = 35), effectively treated by sulfonylureas group (n = 32) , and secondary failure of sulfonylureas group (n = 34). The indexs of insulin resistance of homeostasis model assessment (HOMA-IR), beta-cell insulin secretion of homeostasis model assessment (HOMA-IS), and the acute insulin response (AIRARG) index were calculated. Some statistical comparisons were done among the 4 groups. RESULTS: The indexs of HOMA-IR in each group of Type 2 diabetic patients were all higher than those in NC group (P < 0.01). The AIRARG indexs were obviously lower in Type 2 diabetic patients in different stages than those in NC group (P < 0.01), and the subsequence from the highest to the lowest among the groups of diabetic patients was: the newly diagnosed group, the effectively treated by sulfonylureas group, and the secondary failure of sulfonylureas group (P < 0.01). But there was no significant difference in indexs of HOMA-IS between the newly diagnosed group and the effectively treated by sulfonylureas group. CONCLUSION There is severe insulin resistance in Type 2 diabetic patients in each stage. The variations of early-phase insulin secretion manifest a vary procedure of obvious deterioration by degrees from the newly diagnosed group to the secondary failure of sulfonylureas group in Type 2 diabetic patients.
Adult ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Female ; Humans ; Insulin ; metabolism ; Insulin Resistance ; Insulin Secretion ; Insulin-Secreting Cells ; metabolism ; Male ; Middle Aged ; Sulfonylurea Compounds ; therapeutic use ; Time Factors

Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life. In most cases, the causes are not known. Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K(+) channel have been described in patients with PND. We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to-methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively. After several years of insulin therapy, these patients were managed by oral glibenclamide therapy at a daily dose of 0.8-0.9 mg/kg. Their basal c-peptide levels increased after one week of glibenclamide therapy, and one month later, the insulin and c-peptide levels were in the normal ranges without any episodes of hyper- or hypoglycemia. These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age.
Base Sequence ; C-Peptide/blood ; DNA Mutational Analysis ; Diabetes Mellitus/blood/*drug therapy/genetics ; Female ; Glyburide/*therapeutic use ; Hemoglobin A, Glycosylated/metabolism ; Heterozygote ; Humans ; Hypoglycemic Agents/therapeutic use ; Infant ; Infant, Newborn ; Insulin/blood/*therapeutic use ; Korea ; *Mutation ; Potassium Channels, Inwardly Rectifying/*genetics ; Sulfonylurea Compounds/therapeutic use ; Treatment Outcome

Adult ; Alveolar Bone Loss ; therapy ; Blood Glucose ; metabolism ; Chronic Periodontitis ; blood ; complications ; diagnostic imaging ; therapy ; Dental Scaling ; Diabetes Mellitus, Type 1 ; blood ; complications ; drug therapy ; Diabetes Mellitus, Type 2 ; blood ; complications ; drug therapy ; Humans ; Hypoglycemic Agents ; therapeutic use ; Insulin ; therapeutic use ; Male ; Metformin ; therapeutic use ; Middle Aged ; Patient Education as Topic ; Periodontal Index ; Radiography, Panoramic ; Root Planing ; Sulfonylurea Compounds ; therapeutic use

Neonatal diabetes mellitus (DM) is defined as insulin-requiring DM in the first six months of life. Unlike type 1 DM, it is a monogenic disorder resulting from a de novo mutation in the genes involved in the development of the pancreas, β-cell mass or secretory function. The majority of neonatal DM cases are caused by a heterozygous activating mutation in the KCNJ11 or ABCC8 genes that encode the Kir6.2 and SUR1 protein subunits, respectively, in the KATP channel. Sulphonylurea, a KATP channel inhibitor, can restore insulin secretion, hence offering an attractive alternative to insulin therapy. We report three cases of neonatal DM and their genetic mutations. Two patients were successfully switched over to sulphonylurea monotherapy with resultant improvement in the quality of life and a more stable blood glucose profile. Patients with neonatal DM should undergo genetic evaluation. For patients with KCNJ11 and ABCC8 gene mutation, oral sulphonylurea should be considered.
ATP-Binding Cassette Transporters ; genetics ; Blood Glucose ; metabolism ; Diabetes Mellitus ; genetics ; therapy ; Female ; Genotype ; Heterozygote ; Humans ; Infant ; Infant, Newborn ; Male ; Models, Biological ; Models, Genetic ; Molecular Biology ; Mutation ; Pancreas ; physiology ; Potassium Channels, Inwardly Rectifying ; genetics ; Quality of Life ; Receptors, Drug ; genetics ; Sulfonylurea Compounds ; therapeutic use ; Sulfonylurea Receptors

OBJECTIVETo observe the effect of Yiqi Yangyin Huoxue Tongfu (YYHT) principle in treating diabetes mellitus type 2 of secondary failure to sulfonylurea agents.

METHODSForty patients were randomly divided into two groups, based on the unchanged previous treatment of sulfonylurea agents, Chinese decoction prescribed according to YYHT principle was given to the treated group and rosiglitazone was given to the control group. Changes of insulin sensitivity (SI), insulin response to glucose (IRG), insulin sensitive index (ISI), tumor necrosis factor-alpha (TNF-alpha), endothelin-1 (ET-1), 6-keto-prostaglandin F1alpha(6-keto-PGF1alpha) and thromboxane B2 (TXB2) were observed.

RESULTSThe total effective rate in the treated group was 71.4%, that on improving peripheral insulin resistance was 76.2%, the two parameters were similar to those in the control group. In the treated group, SI, ISI were significantly improved, and TNF-alpha, ET-1 and TXB2 significantly lowered, but no change of IRR was found.

CONCLUSIONApplication of YYHT principle in treating patients with diabetes mellitus type 2 of secondary failure to sulfonylurea agents could alleviate the peripheral resistance to insulin, inhibit TNF-alpha, and protect the vascular endothelial cells.

Adult ; Aged ; Diabetes Mellitus, Type 2 ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Endothelin-1 ; metabolism ; Female ; Humans ; Hypoglycemic Agents ; therapeutic use ; Insulin Resistance ; Male ; Middle Aged ; Phytotherapy ; Sulfonylurea Compounds ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism ; Yin Deficiency ; drug therapy