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Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.
Subject(s)
Adult , Humans , Autoantibodies , C-Peptide , Diabetes Complications , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Diagnosis , Dipeptidyl-Peptidase IV Inhibitors , Glucagon-Like Peptide 1 , Hypoglycemic Agents , Insulin , Insulin Resistance , Islets of Langerhans , Phenotype , Population CharacteristicsABSTRACT
OBJECTIVE:To evaluate the improvement effects of sitagliptin on islet B-cell function in type 2 diabetic patients systematically,and to provide evidenced-based reference. METHODS:Retrieved from PubMed,Cochrane library,EMBase, CJFD,Wanfang database,VIP and CBM,RCTs about sitagliptin alone or combined with routine plan(trial group)vs. placbo alone or combined with routine plan(control group)in the treatment of type 2 diabetes were collected. Two reviewers independent-ly screened studies according to exclusion and inclusion criteria,extracted data,and assessed the methodological quality according to Cochrane Manual 5.1.0. Meta-analysis was performed by using RevMan 5.3 software. RESULTS:A total of 5 RCTs were includ-ed,involving 1253 patients. The result of Meta-analysis showed that changes of islet B cell function index(Homa-B)[sitagliptin alone group:MD=9.21,95%CI(4.16,14.25),P<0.001;drug combination group:MD=7.24,95%CI(0.80,13.68),P=0.03] and changes of insulin resistance index(Homa-IR)[sitagliptin alone group:MD=-0.40,95%CI(-0.44,-0.36),P<0.001;drug combination group:MD=-0.35,95%CI(-0.63,-0.07),P=0.02] of trial group were significantly better than those of control group,with statistical significance. CONCLUSIONS:Sitagliptin shows certain therapeutic efficacy in improving islet B cell func-tion and insulin resistance.
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OBJECTIVE:To observe the effectiveness and safety of liraglutide combined with insulin and glipizide in the treat-ment of subclinical hypothyroidism(SCH)complicated with type 2 diabetes in the elderly patients. METHODS:Totally 82 elderly patients with SCH complicated with type 2 diabetes were selected from our hospital during Dec. 2013-Dec. 2015,and then divided into trial group(40 cases)and control group(42 cases)according to random number table. Control group was given Insulin in-jection+Glipizide tablets. Trial group was additionally given Liraglutide injection 0.6 mg,sc,qd,on the basis of control group. Treatment courses of 2 groups lasted for 12 weeks. The levels of blood glucose [fasting glucose,postprandial 1 h and 2 h glucose,mean of daily differences(MODD),mean amplitude of glycemic excursions(MAGE)],glycosylated hemoglo-bin,body weight,total cholesterol,blood pressure [systolic blood pressure(SBP),diastolic blood pressure(DBP)],thyroid stimulating hormone(TSH)and homeostasis model assessment(HOMA-B)were observed in 2 groups before and after treat-ment. The occurrence of ADR was recorded. RESULTS:Totally 4 patients of control group withdrew from the study,and no one withdrew from the study in trial group. Before treatment,there was no statistical significance in the levels of blood glu-cose,glycosylated hemoglobin,body weight,total cholesterol,blood pressure,TSH and HOMA-B (P>0.05). After treat-ment,body weight and total cholesterol level of trial groups were significantly decreased and lower than those of control group,with statistical significance (P0.05). CONCLUSIONS:Liraglutide com-bined with insulin and glipizide for elderly patients with SCH complicated with type 2 diabetes can effectively reduce blood glucose level,keep blood glucose stable,control the increase of body weight and improve islet B cell function with good safety.
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Objective To study the effects of sulodexide on islet B-cell function in streptozocin induced di-abetic rats. Methods Sprague-Dawley(SD) rats were randomly divided into normal control group (group C), dia-betic group without treatment(group D), and suledexide treatment group(group S), a single dose of streptozotocin were abdominally injected to establish the diabetic rat models. Each animal in sulodexide treated group was addition-ally fed with sulodexide of 10 mg/(kg·d) for 12 weeks,while the remained group (group C and D) were given normal water in the same period. After 12 weeks of treatment, fasting plasma glucose(FPG),fasting plasma insulin (FINS), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C), serum creatinine rates (SCr) and alanine aminotransferase (ALT) were measured. Insulin sensitivity index(ISI) and insulin resistant index (HOMA-IR) were calculated. Results After 12 weeks, the levels of TG, LDL-C and ALT had no significant difference between group D and group S, but were higher than those in group C (P <0.05);There were no significant difference of SCr levels among the three groups. Compared with the group C, APTT, PT, TT and ISI in group D and S were significantly decreased, HOMA-IR were significantly increased (P < 0.05). APTT, PT, TT and ISI in group S had significantly increased compared with that in group D, HOMA-IR was significantly decreased in group S compared with that in group D (P < 0.01). Conclusions Sulodexide can reduce insulin resistant, improve hypercoagulability and insulin sensitiv-ity in streptozocin induced diabetic rats. The effects to blood lipid, liver and renal functions in diabetic rats are not obvious.
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The impact of hypofunction of kidney on evaluating of islets β cell function in patients with type 2 diabetes was investigated. 635 type 2 diabetic patients with normal liver function were grouped using Cockcroft-Gault. Following the decrease in kidney function, blood C-peptide concentration was increased with decreased urinary exeretion of C-peptide(P<0. 05). It is proposed to pay an attention to renal function while evaluating islets β cell function in the patients.
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Objective To study the assiociation of-866G/A polymorphism in the promoter of uncoupling protein 2(UCP2)gene in patients with type 2 diabetes and B-cell function in Han population in Nanjing.Methods For the case-control study,PCR-RFLP method was used to determine the distributions of allele and genotype frequencies of-866G/A polymorphism in the human UCP2 gene in 229 type 2 diabetic patients and 196 normal control subjects.All of the testees accepted oral glucose tolerance test and insulin releasing test to detect B-cell secretion function and insulin sensitivity.Results The distribution of genotype and allele frequencies of-866G/A polymorphism in the promoter of the human UCP2 gene were significantly different between type 2 diabetic patients and normal control subjects(?2=6.555,P=0.038;?2=6.363,P=0.012 respectively).The frequency of A/A genotype and A allele in type 2 diabetic were significantly higher than that in contrast(OR=1.99,OR=1.42 respectively,both P
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Objective To study the change of B-cell function after reduction in plasma free fatty acid(FFA)concentration.Methods All 38 normoglycemic first-degree relatives of type 2 diabetes received a 75 g oral glucose tolerance test(OGTT),before and after acipimox,250 mg orally tid for 5 days.Results Acipimox significantly reduced fasting plasma FFA,HOMA-IR,the incremental glucose area under the curve(AUCg)and the incremental FFA area under the curve(AUCf)during OGTT(P0.05).The increment in ?I30/?G30、?I30??G30-1?HOMA-IR-1 correlated negatively with the decrement in fasting FFA,AUCf(r=-0.39~-0.49,P
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0.05.Conclusion:The prior glucose bolus does not affect the following euglycemic clamp.The Botnia clamp is a useful method for simultaneous independent assessment of insulin secretion and insulin sensitivity.