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Effect of interactions between C peptide levels and insulin treatment on clinical outcomes among patients with type 2 diabetes mellitus.

ABSTRACT: BACKGROUND: A recently halted clinical trial showed that intensive treatment of type 2 diabetes mellitus was associated with increased mortality. Given the phenotypic heterogeneity of diabetes, therapy targeted at insulin status may maximize benefits and minimize harm. METHODS: In this longitudinal cohort study, we followed 503 patients with type 2 diabetes who were free of cardiovascular disease from 1996 until data on mortality and cardiovascular outcomes were censored in 2005. Phenotype-targeted therapy was defined as use of insulin therapy in patients with a fasting plasma C peptide level of 0.2 nmol/L or less and no insulin therapy in patients with higher C peptide levels. RESULTS: The mean age of the cohort was 54.4 (standard deviation 13.1) years, and 56% were women. The mean duration of diabetes was 4.6 years (range 0-35.9 years). Of the 503 patients, 110 (21.9%) had a low C peptide level and 111 (22.1%) were given insulin. Based on their C peptide status, 338 patients (67.2%) received phenotype-targeted therapy (non-insulin-treated, high C peptide level [n = 310] or insulin-treated, low C peptide level [n = 28]), and 165 patients (32.8%) received non-phenotype-targeted therapy (non-insulin-treated, low C peptide level [n = 82] or insulin-treated, high C peptide level [n = 83]). Compared with the insulin-treated, low-C-peptide referent group, the insulin-treated, high-C-peptide group was at a significantly higher risk of cardiovascular events (hazard ratio [HR] 2.85, p = 0.049) and death (HR 3.43, p = 0.043); the risk was not significantly higher in the other 2 groups. These differences were no longer significant after adjusting for age, sex and diabetes duration. INTERPRETATION: Patients with low C peptide levels who received insulin had the best clinical outcomes. Patients with normal to high C peptide levels who received insulin had the worst clinical outcomes. The results suggest that phenotype-targeted insulin therapy may be important in treating diabetes.

SUBMITTER: Ko GT

PROVIDER: S-EPMC2670904 | biostudies-other | 2009 Apr

REPOSITORIES: biostudies-other

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Effect of interactions between C peptide levels and insulin treatment on clinical outcomes among patients with type 2 diabetes mellitus.

Ko Gary T C GT So Wing-Yee WY Tong Peter C PC Chan Wing-Bun WB Yang Xilin X Ma Ronald C RC Kong Alice P AP Ozaki Risa R Yeung Chun-Yip CY Chow Chun-Chung CC Chan Juliana C JC

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20090401 9

<h4>Background</h4>A recently halted clinical trial showed that intensive treatment of type 2 diabetes mellitus was associated with increased mortality. Given the phenotypic heterogeneity of diabetes, therapy targeted at insulin status may maximize benefits and minimize harm.<h4>Methods</h4>In this longitudinal cohort study, we followed 503 patients with type 2 diabetes who were free of cardiovascular disease from 1996 until data on mortality and cardiovascular outcomes were censored in 2005. Ph ...[more]

PMID: 19398738

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Project description:BACKGROUND:Chronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but the long-acting insulin analogues seem beneficial. Several reviews have compared either insulin detemir or insulin glargine to NPH insulin, but research directly comparing both insulin analogues is limited. OBJECTIVES:To assess the effects of insulin detemir and insulin glargine compared with each other in the treatment of type 2 diabetes mellitus. SEARCH STRATEGY:We searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011. SELECTION CRITERIA:All randomised controlled trials comparing insulin detemir with insulin glargine with a duration of 12 weeks or longer were included. DATA COLLECTION AND ANALYSIS:Two authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed. MAIN RESULTS:This review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either insulin detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at the end of trial.Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups.The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups.Insulin detemir was associated with less weight gain. Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions.There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups. AUTHORS' CONCLUSIONS:Our analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.

Project description:IntroductionAlthough the largest improvement in glycemic control occurs within the first 90 days of insulin therapy, little is known about early persistence on insulin therapy. This research aimed to identify predictors of early discontinuation and of subsequent restart of basal or mixture insulin among patients with type 2 diabetes mellitus (T2DM) and to assess the economic cost associated with such behaviors over a 1-year period.MethodsTruven's Health Analytics Commercial Claims and Encounters database was utilized for the study. Logistic regressions were used to examine factors associated with early discontinuation of insulin (basal or mixture) and, among patients who discontinued early, the factors associated with restarting. Cost regressions were estimated using generalized linear models with a gamma distribution and logistic link. Kaplan-Meier survival curves were used to examine time to discontinuation and time to restart among those who discontinued.ResultsMultivariate analyses revealed that patient characteristics, prior healthcare resource utilization, comorbid diagnoses, and type of initiated insulin were associated with early discontinuation of insulin and of restarting among patients who discontinued early. Acute care (hospitalization and emergency room) costs were 9.6% higher among patients who discontinued early (P < 0.001), although outpatient, drug, and total costs were significantly lower among individuals who discontinued early. Among the early discontinuation subgroup, restarting insulin was associated with higher costs. Specifically: 11.3% higher acute care costs (P < 0.001), 24.0% higher outpatient costs (P < 0.001), 80.2% higher drug costs (P < 0.001), and 30.3% higher total costs (P < 0.001), compared to patients who discontinued early but did not restart insulin therapy in the 1-year post-period.ConclusionAmong patients with T2DM who were initiated on insulin therapy, early discontinuation of insulin and its subsequent restart were associated with significantly higher acute care costs, which may signal a more complex and challenging subgroup of patients who tend to be less engaged in outpatient care and may have poorer long-term outcomes.

Project description:IMPORTANCE:Questions remain about the role and durability of bariatric surgery for type 2 diabetes mellitus (T2DM). OBJECTIVE:To compare the remission of T2DM following surgical and nonsurgical treatments. DESIGN, SETTING, AND PARTICIPANTS:In this 3-arm randomized clinical trial conducted at the University of Pittsburgh Medical Center from October 1, 2009, to June 26, 2014, in Pittsburgh, Pennsylvania, outcomes were assessed 3 years after treating 61 obese participants aged 25 to 55 years with T2DM. Analysis was conducted with an intent-to-treat population. INTERVENTIONS:Participants were randomized to either an intensive lifestyle weight loss intervention for 1 year followed by a low-level lifestyle intervention for 2 years or surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) followed by low-level lifestyle intervention in years 2 and 3. MAIN OUTCOMES AND MEASURES:Primary end points were partial and complete T2DM remission and secondary end points included diabetes medications and weight change. RESULTS:Body mass index (calculated as weight in kilograms divided by height in meters squared) was less than 35 for 26 participants (43%), 50 (82%) were women, and 13 (21%) were African American. Mean (SD) values were 100.5 (13.7) kg for weight, 47.3 (6.6) years for age, 7.8% (1.9%) for hemoglobin A1c level, and 171.3 (72.5) mg/dL for fasting plasma glucose level. Partial or complete T2DM remission was achieved by 40% (n?=?8) of RYGB, 29% (n?=?6) of LAGB, and no intensive lifestyle weight loss intervention participants (P?=?.004). The use of diabetes medications was reduced more in the surgical groups than the lifestyle intervention-alone group, with 65% of RYGB, 33% of LAGB, and none of the intensive lifestyle weight loss intervention participants going from using insulin or oral medication at baseline to no medication at year 3 (P?<?.001). Mean (SE) reductions in percentage of body weight at 3 years were the greatest after RYGB at 25.0% (2.0%), followed by LAGB at 15.0% (2.0%) and lifestyle treatment at 5.7% (2.4%) (P?<?.01). CONCLUSIONS AND RELEVANCE:Among obese participants with T2DM, bariatric surgery with 2 years of an adjunctive low-level lifestyle intervention resulted in more disease remission than did lifestyle intervention alone. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01047735.

Project description:BackgroundGlucagon-like peptide analogues are a new class of drugs used in the treatment of type 2 diabetes that mimic the endogenous hormone glucagon-like peptide 1 (GLP-1). GLP-1 is an incretin, a gastrointestinal hormone that is released into the circulation in response to ingested nutrients. GLP-1 regulates glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, and by suppressing glucagon secretion, delayed gastric emptying and promoting satiety.ObjectivesTo assess the effects of glucagon-like peptide analogues in patients with type 2 diabetes mellitus.Search strategyStudies were obtained from electronic searches of The Cochrane Library (last search issue 1, 2011), MEDLINE (last search March 2011), EMBASE (last search March 2011), Web of Science (last search March 2011) and databases of ongoing trials.Selection criteriaStudies were included if they were randomised controlled trials of a minimum duration of eight weeks comparing a GLP-1 analogue with placebo, insulin, an oral anti-diabetic agent, or another GLP-1 analogue in people with type 2 diabetes.Data collection and analysisData extraction and quality assessment of studies were done by one reviewer and checked by a second. Data were analysed by type of GLP-1 agonist and comparison treatment. Where appropriate, data were summarised in a meta-analysis (mean differences and risk ratios summarised using a random-effects model).Main resultsSeventeen randomised controlled trials including relevant analyses for 6899 participants were included in the analysis. Studies were mostly of short duration, usually 26 weeks.In comparison with placebo, all GLP-1 agonists reduced glycosylated haemoglobin A1c (HbA1c) levels by about 1%. Exenatide 2 mg once weekly and liraglutide 1.8 mg reduced it by 0.20% and 0.24% respectively more than insulin glargine. Exenatide 2 mg once weekly reduced HbA1c more than exenatide 10 μg twice daily, sitagliptin and pioglitazone. Liraglutide 1.8 mg reduced HbA1c by 0.33% more than exenatide 10 μg twice daily. Liraglutide led to similar improvements in HbA1c compared to sulphonylureas but reduced it more than sitagliptin and rosiglitazone.Both exenatide and liraglutide led to greater weight loss than most active comparators, including in participants not experiencing nausea. Hypoglycaemia occurred more frequently in participants taking concomitant sulphonylurea. GLP-1 agonists caused gastrointestinal adverse effects, mainly nausea. These adverse events were strongest at the beginning and then subsided. Beta-cell function was improved with GLP-1 agonists but the effect did not persist after cessation of treatment.None of the studies was long enough to assess long-term positive or negative effects.Authors' conclusionsGLP-1 agonists are effective in improving glycaemic control.

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Effect of interactions between C peptide levels and insulin treatment on clinical outcomes among patients with type 2 diabetes mellitus.

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Effect of interactions between C peptide levels and insulin treatment on clinical outcomes among patients with type 2 diabetes mellitus.

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