Clinical characteristics and heterogeneity in patients with ketosis-prone diabetes / 中华内分泌代谢杂志

Objective To investigate the clinical characteristics,peripheral insulin sensitivity,and β-cell function in patients with ketosis-prone diabetes(KPD).Methods Thirty-one patients with newly diagnosed ketosisprone diabetes were admitted to West China Hospital from January 2004 to December 2009.They were divided into 2 groups according to their body mass index (BMI):OB-KPD (BMI ≥ 25 kg/m2,n =22) and Lean-KPD (BMI ＜ 23 kg/m2,n =9).10 patients with newly-onset type 2 diabetes free from ketosis (OB-DM:BMI ≥ 25 kg/m2,n =10) were enlisted as control.Detailed assessments of medical history and symptoms of hyperglycemia were performed.The islet cell antibody (ICA),insulin autoantibody (IAA),anti-glutamic acid decarboxylase antibody (GAD-Ab),fasting plasma glucose,serum insulin,C-peptide and free fat acids concentrations were measured.All of the subjects underwent oral and intravenous glucose tolerance tests,euglycemic-hyperinsulinemia and hyperglycemia clamp test,to evaluate the insulin secretion and insulin sensitivity respectively.Insulin sensitivity was determined by glucose disposal rate (GDR) of steady state during euglycemic clamp and acute insulin secretion was calculated by insulin area under curve(AUCins 0-10 min) during IVGTT.Maximal insulin secretion was determined by glucose infusion rate (GIR) and serum insulin concentration of steady state during hyperglycemic clamp test.Results Age,sex,duration of diabetes were matched among groups.A family history of diabetes was strongly associated with those patients with obesity,compared with lean ketosis prone diabetes(16/22 vs 1/9).GDR was (4.91 ± 1.82) mg · kg 1 · min-1 in subjects with OB-KPD,being lower than that in Lean-KPD patients[(6.26 ± 1.89) mg · kg 1 · min-1] and OB-DM group[(6.78-± 1.69) mg · kg 1 · min-1,P＜0.01].Serum insulin and C-peptide in OB-KPD patients were higher than Lean-KPD patients.Area under the insulin curve [AUCins0-10min (183.86 ± 31.1) mIU/L] and GIR[(2.65 ±1.53) mg · kg-1 · min-1] in OB-KPD patients were lower than those in OB-DM group[(697.06-± 231.9) mIU/L,(6.53 ± 2.21)mg · kg 1 · min-1,P＜0.0 1],but slightly higher than the Lean-KPD group [AUCins0 10min (92.1 ±29.8) mUU/L,GIR (2.55 ± 1.49) mg · kg 1 · min-1,P＜0.05].Glucose disposal rate (GDR) was strongly associated with casual plasma glucose (r =-0.502,P＜0.01),HbA1C(r =-0.553,P＜0.0 1) and FFA eoneentrations (r=-0.504,P＜0.01) on admission.Conclusions Insulin resistance and β-cell dysfunction coexist in all KPD patients.OB-KPD patients exhibit more severe insulin resistance,while Lean-KPD patients have lower insulin secretion.KPD patients had severe hyperglycemia,hypertriglyceridemia,and high plasma FFA levels on admission,suggesting that hyperglycemia and elevated FFA levels could result in serious insulin resistance,β-cell dysfunction,and diabetic ketosis in patients with KPD.

The efficacy and safety of recombinant human insulin injection in the treatment of diabetic patients: a multicenter, randomized, controlled and open-labled clinical trial / 中华内科杂志

Objective A multicenter, randomized, controlled and open-labled clinical trial was performed to compare the efficacy and safety of recombinant human insulin injection ( Yousilin R) and treated with Yousilin R versus Novolin R for 12 weeks respectively. Results Compared with baseline,the levels of glycosylated hemoglobin A1c ( HbA1c ) at the end of 12 weeks treatment decreased from 10. 77% to 7. 72% ( P ＜0. 05 ) in Yousilin R group and from 10. 33% to 7. 62% ( P ＜0. 05 ) in Novolin R group,2-hour postprandial plasma glucose ( 2hPG ) decreased from 15.49 mmol/L to 9. 72 mmol/L ( P ＜ 0. 05 ) in Yousilin R group and from 15.33 mmol/L to 10. 07 mmol/L( P ＜ 0. 05 ) in Novolin R group, and fasting plasma glucose (FPG) decreased from 10. 90 mmol/L to 7. 31 mmol/L( P ＜0. 05 ) in Yousilin R group and from 10. 22 mmol/L to 7.21 mmol/L (P ＜0. 05) in Novolin R group. The changes of HbA1c, 2hPG and FPG from baseline to endpoint in Yousilin R group was similar to those in Novolin R group ( P ＞ 0. 05 ).Furthermore, hypoglycemic events(26. 42% vs 30. 48% ), other adverse events( 13.21%vs 16. 19% ) ,and serious adverse events( 1.89%vs 1.90% )were comparable between Yousilin R and Novolin R groups(P ＞0. 05 ). Conclusions Yousilin R has similar efficacy, safety and compliance profiles to Novolin R group in the treatment of diabetic patients.

Study of metabolic syndrome and insulin secretion function in first-degree relatives of type 2 diabetic patients in a large cohort study in Sichuan province of China / 生物医学工程学杂志

This investigation was directed to the metabolic syndrome and the islet beta-cell secretory function in the first-degree relatives (FDR) of type 2 diabetic patients in Sichuan province. A large cohort study was designed. Totally 1929 subjects were investigated. They were in two groups: FDR group comprising 505 first-degree relatives of type 2 diabetic patients, and Control group comprising 1424 controls without positive family history of Diabetes. Blood pressure, weight, waist, plasma glucose, lipids and insulin were measured. HOMA-IR and HOMA-beta indexes were used to evaluate insulin resistance and beta-cell secretion function. The insulin sensitivity index (ISI) and glucose disposition index (DI) were also used to evaluate insulin resistance. After adjustment for age and sex, HOMA-IR increased, ISI, DI and HOMA-beta decreased in FDR group when compared with controls (P < 0.05). The incidence of co-existed three or more metabolic disorders and metabolic syndrome was higher in FDR group than that in control group (P < 0.05). In FDR group, HOMA-IR increased, HOMA-beta, DI and ISI decreased while the number of co-existing metabolic disorders increased. But when the number of co-existing metabolic disorders > or = 4, HOMA-IR increased no longer and ISI decreased no more. Metabolic disorders occurred more frequently in FDR of diabetic patients than those in individuals without positive family history. As the number of co-existing metabolic disorders increased, the beta-cell secretion function and insulin sensitivity became worse. Our study indicated that it is necessary to keep on monitoring the metabolic index in FDR of type 2 diabetes and provide early preventive interventions.

Changes of leptin, tumor necrosis factor-alpha, neuropeptide Y levels and their association with insulin resistance and insulin secretion function in normal glucose tolerant first-degree relatives of familial type 2 diabetic pedigrees / 生物医学工程学杂志

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.

I27L Polymorphism in hepatocyte nuclear factor-lot gene and type 2 diabetes mellitus: a meta-analysis of studies about orient population [Chinese and Japanese]

The aim of the study was to investigate the relationship between I27L variant of HNF-loc gene and type 2 diabetes mellitus [T2DM] in an/the oriental population. We recruited 149 T2DM patients and 96 non-diabetes controls from China. The I27L polymorphism in HNF-la gene was detected by PCR-RFLP analysis. A mete-analysis of previously published studies on I27L and T2DM of orient population and our new study was performed. Databases of MEDLINE, CBM, and the Cochrane Library [CD-ROM] were electronically searched from January 1980 to April 2008. Analysis was performed by RevMan 4.2 software which was downloaded from website of Cochrane collaboration. [1]. The genotype distribution of I27L/exonl polymorphism in the HNF-loe gene was in Hardy-Weinberg equilibrium [chi[2] = 2.34, 0.05 < P< 0.1]. The IL, LL genotype frequencies and L allelic frequency were slightly higher in T2DM group than in controls [0.52, 0.14 and 0.40 in T2DM vs. 0.49, 0.08 and 0.33 in controls], but the difference were not statistically significant, which indicated that 27L variant did not increase the risk of T2DM in our small sample Chinese population. [2]. Three published studies concerning the Chinese population, two studies involving the Japanese population and our present study, providing information on a total of 1225 unique subjects, were included in the meta-analysis. The results showed that the 271 variant increased the prevalence of T2DM [OR 1.22, 95% CI 1.03-1.44, p = 0.02]. I27L polymorphism in the HNF-1 alpha gene increases the risk of T2DM in the orient population [Chinese and Japanese]

Combination of glucotoxicity and lipitoxicity impairs pancreatic β-cell function / 中华内分泌代谢杂志

The effects of elevated levels of glucose and (or) free fatty acids on insulin secretion were studied in obese rats by intravenous glucose tolerance test and isolated pancreas perfusinn. The results showed that both glucose- and arginine-stimulated insulin secretions were severely impaired by glucolipotoxicity and the production of ketone was increased dramatically.

Elevated circulating free fatty acids level causes pancreatic islet β-cell dysfunction via oxidative stress / 中华内分泌代谢杂志

Objective To evaluate the effects of elevated circulating free fatty acids (FFA) level on basal and glucose stimulated insulin secretion (GSIS) of islet β-cell and to explore the pathophysiological link between FFA and impaired β-cell dysfunction. Methods Male SD rats underwent infusions with normal saline (C group), intralipid+heparin (FFA group) and N-acetylcysteine+FFA (NAC group) for 2-4 days. Insulin secretion from pancreatic tissues was evaluated during intravenous glucose tolerance test and isolated pancreas perfasion test at the end of 2 and 4 days infusion. Results After 2 days infusion, the basal insulin secretion from isolated perfused pancreas was increased in FFA group [(55.5±19.4 vs 27.4±6.7) mU/L, P<0.01], but the response to 16.7 mmol/L glucose in isolated perfased pancreas was similar in FFA and C groups. The peak value during GSIS was inhibited by 4 days FFA infusion [(46.8±33.0 vs 214.7±27.4)mIU/L,P<0.05]. GSIS was also decreased in FFA group compared with C group in IVGTr. After interfered with NAC, GSIS was partly recovered [(165.4± 14.8)mIU/L, P<0.01]. Conclusion Elevated circulating FFA levels may contribute to the abnormality of pancreatic islet β-cell through oxidative stress.

Relationship between insulin resistance and oxidative stress caused by elevated concentration of free fatty acids / 中华内分泌代谢杂志

The relationship between elevated concentration of circulating free fatty acids (FFA) and insulin resistance wag studied,and the pathophysiological mechanism of insulin resistance,especially focused on oxidative stress,was explored.It was found that the elevated circulating FFA level led to insulin resistance in rats, which was partly caused by oxidative stress,and that antioxidative treatment was able to reverse the pathologic change.As a result of enhancing reactive oxygen species production[(886±105 vs 427±42)mmol/L,P<0.05] and disrupting antioxidant[(272±47 vs 561±36)μmol/L,P<0.05],elevated concentration of FFA may induce oxidative stress.

Absence of association of the L296Q polymorphism in the cholesteryl ester transfer protein gene with type 2 diabetes mellitus in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between L296Q polymorphism in the cholesterol ester transfer protein(CETP)gene and type 2 diabetes mellitus(T2DM)and blood lipids.</p><p><b>METHODS</b>Plasma glucose and lipid levels were measured in a total of 303 subjects recruited from the West China Hospital of Sichuan University. The subjects were divided into 4 groups according to the levels of plasma glucose and triglyceride, namely T2DM with hypertriglyceridemia group, group of T2DM with normal triglyceride, group of hypertriglyceridemia without DM and group of normal controls, respectively. Genotypes of L296Q polymorphism in the CETP gene of all subjects were analyzed by real-time fluorescent quantitative PCR(FQ-PCR).</p><p><b>RESULTS</b>No significant differences were observed in the frequencies of genotypes LL and LQ and the 296Q allele among the four groups (chi-square=3.459, P>0.05; chi-square=3.155, P>0.05, respectively), nor the frequencies of genotypes LL and LQ between the T2DM and non-T2DM, or plasma lipid levels between the 296Q allele carriers and those of genotype LL.</p><p><b>CONCLUSION</b>No association was found between the L296Q polymorphism in the CETP gene and T2DM as well as plasma lipid levels in various groups of Chinese in this study.</p>

Effect of pioglitazone treatment on components of serum free fatty acid in type 2 diabetic patients / 中华内分泌代谢杂志

Components of free fatty acids (FFA) were examined by reverse high performance liquid chromatography in 25 patients with type 2 diabetes and 25 control subjects.The changes in components of FFA were observed before treatment, at 3 months and 1 year after treatment with pioglitazone in type 2 diabetic patients.The serum lauric acid, myristic acid and stearic acid levels were much higher in the diabetic patients than those in control subjects.Pioglitazone could decrease the levels of these fatty acids in the patients with type 2 diabetes mellitus.