Pioglitazone does not affect the risk of kidney cancer in patients with type 2 diabetes

Objective

To investigate whether pioglitazone treatment of patients with type 2 diabetes mellitus was associated with an increased risk of kidney cancer.

Methods

The reimbursement databases of all Taiwanese patients with type 2 diabetes who received oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006, and a total of 1,093,675 patients with type 2 diabetes were followed up for kidney cancer incidence until the end of 2009. The incidences of kidney cancer among patients who had and had not received pioglitazone, as well as among subgroups of those treated with pioglitazone (sorted by time since starting pioglitazone, duration of treatment and cumulative dose) were calculated and hazard ratios (HRs) estimated by Cox regression analysis.

Results

Of the 1,093,675 patients, 58,172 (5.3%) had and 1,035,503 (94.7%) had not received pioglitazone, with incident kidney cancer developing in 208 (0.36%) and 3304 (0.32%) patients, respectively, and a respective incidence of 97.7 and 90.5 per 100,000 person-years. Pioglitazone and kidney cancer were not significantly associated in unadjusted (HR 1.04; 95% confidence interval (CI), 0.90–1.20), age-sex-adjusted (HR 1.09; 95% CI, 0.95–1.25), and fully adjusted (HR 1.09; 95% CI, 0.94–1.26) models. None of the dose-response parameters showed a significant trend of risk association, with all P-trends >0.10.

Conclusions

Pioglitazone does not affect the risk of kidney cancer.     

Insulin Therapy and Colorectal Adenoma Risk Among Patients with Type 2 Diabetes Mellitus: A Case-Control Study in Korea

Purpose Patients with Type 2 diabetes mellitus may be at increased colorectal adenoma and cancer risk. Moreover, chronic insulin therapy may increase the risk of colorectal cancer among patients with Type 2 diabetes mellitus. We investigated to determine whether insulin therapy might increase the risk of colorectal adenoma among clinically confirmed patients with Type 2 diabetes mellitus. Methods We conducted a retrospective study among patients with Type 2 diabetes mellitus who underwent total colonoscopy between January 2003 and July 2006 at Hallym University Sacred Heart Hospital. Among them (n = 325), patients with histologically confirmed colorectal adenomas (n = 100) and the same number of controls matched by age and sex were selected and analyzed. Results Adenoma cases showed significantly higher rate of chronic insulin therapy (more than 1 year) than controls (P = 0.018). In multivariate regression analysis, patients who received chronic insulin therapy had three times the risk of colorectal adenoma compared with patients who received no insulin (odds ratio, 3; 95 percent confidence interval, 1.1–8.9; P = 0.04). Conclusions Chronic insulin therapy was associated with increased colorectal adenoma risk among Type 2 diabetes mellitus patients. This result may provide a need for more intensive colorectal cancer screening program in patients with Type 2 diabetes mellitus, especially those who receive chronic insulin therapy.     

Type 2 diabetes mellitus and the risk of colorectal cancer.

BACKGROUND & AIMS: Type 2 diabetes mellitus might increase the risk of colorectal cancer on the basis of chronic hyperinsulinemia and hyperglycemia. However, epidemiologic evidence for this association is inconclusive. We conducted a population-based study to clarify this association. METHODS: We conducted a case-control study in the United Kingdom General Practice Research Database. Cases included all patients with incident colorectal cancer diagnoses (n = 10,447). Up to 10 control subjects were selected for each case, matching on year of birth, enrollment date, and duration of database follow-up. The exposure of interest was type 2 diabetes mellitus. Odds ratios (ORs) were calculated by using conditional logistic regression. RESULTS: A prior diagnosis of type 2 diabetes mellitus was associated with a modestly increased risk of colorectal cancer (OR, 1.42; 95% confidence interval [CI], 1.25-1.62). The association between type 2 diabetes mellitus and colorectal cancer was observed in both men (OR, 1.36; 95% CI, 1.16-1.61) and women (OR, 1.38; 95% CI, 1.14-1.67). The risk increase was observed in both colon (OR, 1.45; 95% CI, 1.25-1.70) and rectal (OR, 1.34; 95% CI, 1.08-1.68) cancers. CONCLUSIONS: Type 2 diabetes mellitus is associated with an increased risk of colorectal cancer. The risk increase is present in both sexes, as well as in both colonic and rectal cancers.     

Long-acting insulin analogues and the risk of diabetic retinopathy among patients with type 2 diabetes: A population-based cohort study

Aim

To determine whether the use of long-acting insulin analogues is associated with an increased risk of incident diabetic retinopathy (DR) among patients with type 2 diabetes.

Methods

Using data from the Clinical Practice Research Datalink Aurum, this retrospective, population-based cohort study included patients with type 2 diabetes who initiated a long-acting insulin analogue (glargine, detemir, degludec) or Neutral Protamine Hagedorn (NPH) insulin. The primary outcome was incident DR. We used Cox proportional hazards models with inverse probability of treatment weighting to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DR with insulin analogues versus NPH insulin.

Results

There were 66 280 new users of long-acting insulin analogues and 66 173 new users of NPH insulin. The incidence rate of DR was 101.7 per 1000 person-years (95% CI, 98.7-104.8) for insulin analogues and 93.2 (95% CI, 90.0-96.5) per 1000 person-years for NPH insulin. Compared with the current use of NPH insulin, insulin analogues were not associated with the risk of incident DR (HR 1.04, 95% CI, 0.99-1.09). The adjusted HRs were 0.84 (95% CI, 0.66-1.07) for proliferative DR and 1.02 (95% CI, 0.97-1.08) for non-proliferative DR.

Conclusions

Compared with NPH insulin, long-acting insulin analogues were not associated with the risk of incident DR among patients with type 2 diabetes. This finding provides important reassurance regarding the safety of long-acting insulin analogues with respect to incident DR.     

Cancer mortality reduction and metformin: a retrospective cohort study in type 2 diabetic patients

Aims: Few studies suggest that metformin decreases cancer mortality in type‐2 diabetic patients (T2DP). We explored the association between the type and duration of antidiabetic therapies and cancer and other‐than‐cancer mortality in a T2DP cohort, taking into account the competing risks between different causes of death and multiple potential confounding effects. The mortality rates were compared with the general population from the same area. Methods: In 1995, all T2DP (n = 3685) at our diabetes clinic in Turin (～12% of all T2DP in the city), without cancer at baseline, were identified. Vital status was assessed after a mean 4.5‐year follow‐up. Results: Metformin users had greater adiposity, while insulin users had more co‐morbidities. All‐cause‐ and cancer‐related deaths occurred in: 9.2 and 1.6% of metformin users, 13.1 and 3.0% of sulfonylureas users and 26.8 and 4.8% of insulin users, respectively. In a Cox regression model for competing risks, adjusted for propensity score, metformin users showed a lower cancer mortality risk [hazard ratio (HR) = 0.56; 95% confidence interval (CI) 0.34–0.94], while insulin was positively associated with other‐than‐cancer mortality (HR = 1.56; 95%CI 1.22–1.99). Each 5‐year metformin exposure was associated with a reduction in cancer death by 0.73, whereas every 5‐year insulin exposure was associated with 1.25‐fold increase in other‐than‐cancer death. Standardized mortality ratios for cancer and other‐than‐cancer mortality in metformin users were 43.6 (95%CI 25.8–69.0) and 99.1 (95%CI 79.3–122.5), respectively, in comparison with the general population. Conclusions: Metformin users showed a lower risk of cancer‐related mortality than not users or patients on diet only; this may represent another reason to choose metformin as a first‐line therapy in T2DP.     

Cholecystectomy and the risk of colorectal cancer

OBJECTIVES: Cholecystectomy has been implicated as a possible risk factor for colorectal cancer. However, the clinical evidence and the underlying mechanism for this association are still inconclusive. We conducted a population-based study to further clarify this association. METHODS: We conducted a retrospective cohort study among all patients aged 40 yr or older in the General Practice Research Database from the United Kingdom. We excluded patients with <1 yr of colorectal cancer-free database follow-up as well as those patients who developed colorectal cancer within 1 yr after their cholecystectomies. Crude and adjusted incidence rate ratios (IRRs) were determined using Poisson regression. RESULTS: The incidence rate of colorectal cancer among cholecystectomy patients (n = 55,960) was 119 (95% CI: 106-133) per 100,000 person-years, compared to 86 (95% CI: 83-90) per 100,000 person-years among patients without a cholecystectomy (n = 574,668). Among the covariates examined, only sex and age were significant confounders and were included in the adjusted analyses. The adjusted IRR of colorectal cancer associated with cholecystectomy was 1.32 (95% CI: 1.16-1.48, p < 0.001). The positive association was present for colon cancer (adjusted IRR 1.51, 95% CI: 1.30-1.74, p < 0.001), but not for rectal cancer (adjusted IRR 1.00, 95% CI: 0.85-1.17, p= 0.99). The pattern of association was similar in men versus women. A similar association with colon cancer was observed for cholelithiasis. CONCLUSIONS: Cholecystectomy is associated with a modestly increased risk of colon cancer but not for rectal cancer. Lithogenic bile could be the underlying mechanism.     

Insulin use and increased risk of mortality in type 2 diabetes: a cohort study

Aim: To compare population‐based rates of all‐cause and cardiovascular (CV) mortality in newly treated patients with type 2 diabetes according to levels of insulin exposure. Methods: Using the administrative databases of Saskatchewan Health, 12272 new users of oral antidiabetic therapy were identified between 1991 and 1996 and grouped according to cumulative insulin exposure based on total insulin dispensations per year: no exposure (reference group); low exposure (0 to <3); moderate exposure (3 to <12) and high exposure (≥12). Time‐varying multivariable Cox proportional hazards models were used to examine the relationship between insulin exposure and all‐cause, CV‐related and non‐vascular mortality after adjustment for demographics, medications and comorbidities. Results: Average age was 65 (s.d. 13.9) years, 45% were female, and mean follow‐up was 5.1 (s.d. 2.2) years. In total, 1443 (12%) subjects started insulin, and 2681 (22%) deaths occurred. The highest mortality rates were in the high exposure group; 95 deaths/1000 person‐years compared with 40 deaths/1000 person‐years in the no exposure group [unadjusted hazard ratio (HR): 2.32; 95% confidence interval (CI): 1.96–2.73]. After adjustment, we observed a graded risk of mortality associated with increasing exposure to insulin: low exposure [adjusted HR (aHR): 1.75; 95% CI: 1.24–2.47], moderate exposure (aHR: 2.18; 1.82–2.60) and high exposure (aHR: 2.79; 2.36–3.30); p = 0.005 for trend. Analyses restricted to CV‐related (p = 0.042 for trend) and non‐vascular (p = 0.004 for trend) mortality showed virtually identical results. Conclusions: We observed a significant and graded association between mortality risk and insulin exposure level in an inception cohort of patients with type 2 diabetes that persisted despite multivariable adjustment.     

Gallstones, a cholecystectomy, chronic pancreatitis, and the risk of subsequent pancreatic cancer in diabetic patients: a population-based cohort study

Background

The causal association between diabetes and pancreatic cancer remains unclear in Asian populations. This study examined whether gallstones, a cholecystectomy, chronic pancreatitis and the treatment of antidiabetic agents affect the risk of subsequent pancreatic cancer for patients with diabetes in a Taiwanese population.

Methods

Using claims data from the universal health insurance program in Taiwan, 449,685 newly diagnosed diabetic cases among insured people from 2000 to 2003 were identified as the case group. The comparison group, matched for gender, age, and the index year of the diabetes cohort, consisted of 325,729 persons without diabetes. Pancreatic cancer incidence was measured in both groups until the end of 2008. Other risk factors associated with this cancer were also measured.

Results

The incidence of pancreatic cancer in the diabetic cohort was 2-fold greater than that in the comparison group (1.46 vs. 0.71 per 10,000 person-years) with an adjusted hazard ratio (HR) of 1.75 [95 % confidence interval (CI) 1.45–2.10]. The risk slightly increased for diabetic patients with gallstones, cholecystitis, and a cholecystectomy (HR 1.92, 95 % CI 1.18–3.11), but greatly increased for those with comorbidity of chronic pancreatitis (HR 22.9, 95 % CI 12.6–41.4). Pancreatic cancer risk also increased significantly for those patients who used more insulin for treating diabetes (OR 2.20, 95 % CI 1.40–3.45).

Conclusion

Our data suggest that the risk of pancreatic cancer is moderately increased in patients with diabetes, especially those using insulin therapy. The risk is greatly increased for diabetic patients with chronic pancreatitis.     

Exogenous insulin use and hypertension in adult patients with type 2 diabetes mellitus

BACKGROUND: Endogenous hyperinsulinemia, along with insulin resistance, is associated with hypertension. This study investigated the link between exogenous insulin use and hypertension in patients with type 2 diabetes mellitus. METHODS: Using national health insurance records in Taiwan, data from 87,850 adult patients with type 2 diabetes mellitus were collected cross-sectionally with retrospective recall for onset of events. Data were analyzed to evaluate the strength of association, consistency, dose-response relationship, and temporality between exogenous insulin use and hypertension. RESULTS: There were 5927 insulin users, who were characterized by being 1 year older in age, female preponderance, longer duration of diabetes, slightly lower body mass index, and less smoking but higher prevalence of hypertension with higher blood pressure. After adjustment for age, sex, body mass index, duration of diabetes, smoking, and parental hypertension, the odds ratios (95% confidence interval [CI]) for hypertension for patients using insulin for less than 5 years, 5 to 9 years, and 10 years or more were 1.14 (95% CI, 1.06-1.23), 1.35 (95% CI, 1.18-1.54), and 1.46 (95% CI, 1.24-1.74), respectively, compared with nonusers. In insulin users who did not have hypertension at the start of insulin use, the respective odds ratios for those using insulin for 5 to 9 years and 10 years or more were 1.5 (95% CI, 1.25-1.80) and 2.15 (95% CI, 1.72-2.70), respectively, compared with those using insulin for less than 5 years. CONCLUSIONS: In patients with type 2 diabetes mellitus, insulin users are at higher risk for development of hypertension. These observational data suggest the need for further study of the relationship between exogenous insulin use and hypertension.     

Sulphonylureas versus metformin and the risk of ventricular arrhythmias among people with type 2 diabetes: A population-based cohort study

Aim

To determine whether the use of sulphonylurea monotherapy, compared with metformin monotherapy, is associated with an increased risk of ventricular arrhythmia (VA) among patients initiating pharmacotherapy for type 2 diabetes.

Research Design and Methods

We conducted a population-based cohort study using electronic health data extracted from the UK's Clinical Practice Research Datalink Aurum. Using the active comparator, new-user cohort design, we compared rates of VA among patients aged 18 years or older using sulphonylurea monotherapy with those using metformin monotherapy as their initial pharmacological treatment for type 2 diabetes from April 1998 to December 2019. We used a Cox proportional hazards model with inverse probability of treatment weighting by propensity score to estimate the adjusted hazard ratio (aHR) and a corresponding bootstrap 95% confidence interval (CI) for VA with sulphonylurea monotherapy versus metformin monotherapy.

Results

The cohort included 92 638 new users of sulphonylurea and 506 882 new users of metformin. A total of 279 VA events occurred among sulphonylurea users (rate per 10 000 person-years: 25.5, 95% CI: 22.7 to 28.7) and 1537 VA events occurred among metformin users (rate per 10 000 person-years: 18.5, 95% CI: 17.6 to 19.5). Compared with metformin, sulphonylureas were associated with an increased risk of VA (aHR: 1.42, 95% CI: 1.18 to 1.69).

Conclusions

Sulphonylureas are associated with an increased risk of VA when used as first-line therapy for type 2 diabetes relative to metformin use. This increased risk should be considered when prescribing sulphonylureas as an initial treatment for type 2 diabetes.     

The influence of glucose-lowering therapies on cancer risk in type 2 diabetes

Aims/hypothesis  The risk of developing a range of solid tumours is increased in type 2 diabetes, and may be influenced by glucose-lowering therapies. We examined the risk of development of solid tumours in relation to treatment with oral agents, human insulin and insulin analogues. Methods  This was a retrospective cohort study of people treated in UK general practices. Those included in the analysis developed diabetes >40 years of age, and started treatment with oral agents or insulin after 2000. A total of 62,809 patients were divided into four groups according to whether they received monotherapy with metformin or sulfonylurea, combined therapy (metformin plus sulfonylurea), or insulin. Insulin users were grouped according to treatment with insulin glargine, long-acting human insulin, biphasic analogue and human biphasic insulin. The outcome measures were progression to any solid tumour, or cancer of the breast, colon, pancreas or prostate. Confounding factors were accounted for using Cox proportional hazards models. Results  Metformin monotherapy carried the lowest risk of cancer. In comparison, the adjusted HR was 1.08 (95% CI 0.96–1.21) for metformin plus sulfonylurea, 1.36 (95% CI 1.19–1.54) for sulfonylurea monotherapy, and 1.42 (95% CI 1.27–1.60) for insulin-based regimens. Adding metformin to insulin reduced progression to cancer (HR 0.54, 95% CI 0.43–0.66). The risk for those on basal human insulin alone vs insulin glargine alone was 1.24 (95% CI 0.90–1.70). Compared with metformin, insulin therapy increased the risk of colorectal (HR 1.69, 95% CI 1.23–2.33) or pancreatic cancer (HR 4.63, 95% CI 2.64–8.10), but did not influence the risk of breast or prostate cancer. Sulfonylureas were associated with a similar pattern of risk as insulin. Conclusions/interpretation  Those on insulin or insulin secretagogues were more likely to develop solid cancers than those on metformin, and combination with metformin abolished most of this excess risk. Metformin use was associated with lower risk of cancer of the colon or pancreas, but did not affect the risk of breast or prostate cancer. Use of insulin analogues was not associated with increased cancer risk as compared with human insulin.     

Chronic proton pump inhibitor therapy and the risk of colorectal cancer

BACKGROUND & AIMS: Chronic acid suppression by proton pump inhibitor therapy can lead to hypergastrinemia. Because existing evidence suggested an association between hypergastrinemia and colorectal cancer, we examined whether long-term proton pump inhibitor use is associated with an increased risk of colorectal cancer in a population-representative cohort. METHODS: We conducted a nested case-control study among patients 50 years of age and older and with > or =5 years of colorectal cancer-free initial follow-up in the General Practice Research Database (1987-2002) from the United Kingdom. Cases consisted of all patients with an incident diagnosis of colorectal cancer. Using incidence density sampling, up to 10 controls were matched with each case on practice site and both duration and calendar time of follow-up before the index date. The primary exposure of interest was > or =5 years of cumulative proton pump inhibitor therapy. We assessed the presence of duration-response and dose-response effects. RESULTS: We identified 4432 incident colorectal cancer cases and 44,292 controls. The adjusted odds ratio for > or =5 years of proton pump inhibitor exposure was 1.1 (95% confidence interval, 0.7-1.9). Among high-dose proton pump inhibitor users (ie, > or =1.5 defined daily doses/day), there was a nonstatistically significant trend toward an increased risk with increasing duration of use (test for trend, P = .2). However, patients with pernicious anemia were not at increased risk for colorectal cancer (adjusted odds ratio, 0.9; 95% confidence interval, 0.6-1.3). CONCLUSIONS: Long-term proton pump inhibitor therapy at a regular dose is not associated with a significantly increased risk of colorectal cancer.     

Impacts of early insulin treatment vs glimepiride in diabetic patients with background metformin therapy: A nationwide retrospective cohort study

Type 2 diabetes mellitus (T2DM) is a progressive disease. After metformin failure, the addition of insulin or sulfonylureas might increase the risk of hypoglycemia and cardiovascular (CV) morbidity. Here, the risk of all-cause mortality was compared between early insulin treatment and glimepiride use in T2DM patients with background metformin therapy.We conducted a 9-year retrospective cohort study from the population-based National Health Insurance Research Database in Taiwan. A total of 2054 patients with T2DM under insulin or glimepiride treatment were enrolled during 2004 to 2012. Overall event rates of all-cause mortality were compared between 1027 insulin users and 1027 matched glimepiride users.After the propensity score matching, the mortality rates were 72.5 and 4.42 per 1000 person-years for insulin users and glimepiride users. The adjusted hazard ratio of mortality was 14.47 (95% CI: 8.64–24.24; P value <.001) as insulin compared with glimepiride users. The insulin users had significantly higher risk of CV death (adjusted hazard ratio 7.95, 95% CI 1.65–38.3, P = .01) and noncardiovascular death (adjusted hazard ratio 14.9, 95% CI 8.4–26.3, P < .001).The nationwide study demonstrated that metformin plus insulin therapy was associated with higher risk of all-cause mortality.     

Maternal type 1 diabetes reduces the risk of islet autoantibodies: relationships with birthweight and maternal HbA1c

AIMS/HYPOTHESIS: The risk of type 1 diabetes is reduced in the children of mothers with type 1 diabetes compared with children of fathers with type 1 diabetes. We asked whether children of mothers with type 1 diabetes also have a decreased risk of developing islet autoantibodies, and which factors associated with maternal diabetes contribute to a reduced islet autoantibody risk in offspring. METHODS: Singleton offspring of a mother (n = 1,008) or father with type 1 diabetes (n = 578) from the BABYDIAB study were included. Children were followed from birth for the development of islet autoantibodies defined as two or more autoantibodies to insulin, glutamic acid decarboxylase or insulinoma antigen 2 in two or more blood samples. RESULTS: Islet autoantibody risk was lower in children of mothers with type 1 diabetes (5 year risk, 3.2% vs 5.7% in children of fathers with type 1 diabetes; p = 0.04). Among factors that differed between pregnancies from mothers with and without type 1 diabetes, birthweight was associated with islet autoantibody risk. Risk was reduced in children with birthweights in the lower (adjusted HR 0.33; 95% CI 0.14-0.75; p = 0.009) and upper (HR 0.45; 95% CI 0.21-0.97; p = 0.04) tertiles compared with the middle tertile. A sub-analysis of maternal HbA(1c) suggested that moderately elevated third trimester maternal HbA(1c) was also associated with a reduced islet autoantibody risk in children of mothers with type 1 diabetes (5.7-7%; HR 0.38; 95% CI 0.15-0.96; p = 0.04 vs children of mothers with HbA(1c) < 5.7%). CONCLUSIONS/INTERPRETATION: The risk of islet autoimmunity is modified by maternally influenced events such as birthweight.     

A prospective study of cigarette smoking and the incidence of diabetes mellitus among US male physicians

PURPOSE: To determine the association between cigarette smoking and the incidence of type 2 diabetes mellitus. SUBJECTS AND METHODS: We studied 21,068 US male physicians aged 40 to 84 years in the Physicians' Health Study who were initially free of diagnosed diabetes mellitus, cardiovascular disease, and cancer. Information about cigarette smoking and other risk indicators was obtained at baseline. The primary outcome was reported diagnosis of type 2 diabetes mellitus. RESULTS: During 255,830 person-years of follow-up, 770 new cases of type 2 diabetes mellitus were identified. Smokers had a dose-dependent increased risk of developing type 2 diabetes mellitus: compared with never smokers, the age-adjusted relative risk was 2.1 (95% confidence interval [CI]: 1.7 to 2.6) for current smokers of > or = 20 cigarettes per day, 1.4 (95% CI: 1.0 to 2.0) for current smokers of <20 cigarettes per day, and 1.2 (95% CI: 1.0 to 1.4) for past smokers. After multivariate adjustment for body mass index, physical activity, and other risk factors, the relative risks were 1.7 (95% CI: 1.3 to 2.3) for current smokers of > or = 20 cigarettes per day, 1.5 (95% CI: 1.0 to 2.2) for current smokers of <20 cigarettes per day, and 1.1 (95% CI: 1.0 to 1.4) for past smokers. Total pack-years of cigarette smoking was also associated with the risk of type 2 diabetes mellitus (P for trend <0.001). CONCLUSIONS: These prospective data support the hypothesis that cigarette smoking is an independent and modifiable determinant of type 2 diabetes mellitus.     

Predictors of glycemic control after decline of insulin therapy by patients with type 2 diabetes

AimDecline of insulin therapy by patients is common but poorly investigated. We conducted this study to determine patient and treatment characteristics predictive of glycemic control after declining clinician recommendation to initiate insulin therapy.MethodsWe retrospectively studied adults with type 2 diabetes mellitus treated at two academic medical centers between 1993 and 2014 who declined their healthcare provider recommendation to initiate insulin.ResultsIn a multivariable analysis of 300 study patients adjusted for demographics, comorbidities and clustering within providers, higher baseline HbA1c (OR 1.85; 95% CI 1.40 to 2.39; p < 0.001) and lifestyle changes (OR 8.39; 95% CI 3.26 to 21.55; p < 0.001) were associated with greater, while non-adherence to diabetes medications (OR 0.014; 95% CI 0.0025 to 0.085; p < 0.001) and discontinuation of a non-insulin diabetes medication (OR 0.30; 95% CI 0.11 to 0.80; p = 0.016) were associated with lower probability of HbA1c decrease after declining insulin therapy.ConclusionWe identified patient characteristics and treatment strategies associated with success and failure of glycemic control after insulin therapy decline by the patient. This information can assist in selection of optimal therapeutic approaches for these individuals.     

Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease

AIM： To explore the association between hepatocellular carcinoma （HCC） and type 2 diabetes mellitus, describe the temporal relations between the onset of diabetes and the development of HCC and evaluate the possible effects of antidiabetic therapy on HCC risk,METHODS： We recruited 465 HCC patients, 618 with cirrhosis and 490 control subjects. We evaluated the odds ratio （OR） for HCC by univariate and multivariate analysis. Moreover, OR for HCC in diabetic subjects treated with insulin or sulphanylureas and with metformin were calculated.RESULTS： The prevalence of diabetes mellitus was 31.2% in HCC, 233% in cirrhotic patients and 12.7% in the Control group. By univariate and multivariate analysis, the OR for HCC in diabetic patients were respectively 3.12 （CI 2.2-4.4, P 〈 0.001） and 2.2 （CI 1.2-4.4, P = 0.01）. In 84.9% of cases, type 2 diabetes mellitus was present before the diagnosis of HCC. Moreover, we report an OR for HCC of 2.99 （CI 1.34-6.65, P = 0.007） in diabetic patients treated with insulin or sulphanylureas, and an OR of 0.33 （CI 0.1-0.7, P = 0.006） in diabetic patients treated with metformin.CONCLUSION： Our study confirms that type 2 diabetes mellitus is an independent risk factor for HCC and pre-exists in the majority of HCC patients. Moreover, in male patients with type 2 diabetes meUitus, our data shows a direct association of HCC with insulin and sulphanylureas treatment and an inverse relationship with metformin therapy.     

Metformin associated with lower mortality in diabetic patients with early stage hepatocellular carcinoma after radiofrequency ablation

Background and Aim: Type 2 diabetes increases the risk of cancer development and mortality. However, antidiabetic treatment with metformin can reduce the risk of cancer. We studied whether metformin users among diabetic patients with early hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) would have a favorable survival compared with those without metformin treatment. Methods: A total of 135 patients with early stage HCC having 162 tumors underwent RFA. Among them, 53 patients were diabetic, including 21 metformin users and 32 patients without metformin treatment. Results: Diabetic patients had an inferior survival rate compared with nondiabetic patients (1 year, 82.8% vs 93.9%; 3 years, 55.1% vs 80.2%; 5 years, 41.3% vs 64.7%; P = 0.004). With regards to antidiabetic treatments, metformin users had better survival outcome (adjusted hazard ratio [HR] 0.24; 95% confidence interval [CI], 0.07–0.80; P = 0.020) compared to patients without metformin treatment after adjustments for potential confounders. Sulfonylureas and insulin exposures did not achieve significant conclusions. For the whole studied population including nondiabetic and diabetic patients, the multivariate analysis revealed that maximum tumor size more than 2.5 cm (HR, 3.49; 95% CI, 1.74–6.99; P < 0.001) and diabetic patients without metformin treatment (HR, 3.34; 95% CI, 1.67–6.71, P = 0.001) were independent explanatory variables associated with unfavorable survival. Conclusions: Metformin users among diabetic patients with HCC undergoing RFA had a favorable overall survival compared with patients without metformin treatment.     

Comparison of outcomes using sirolimus-eluting stenting in diabetic versus nondiabetic patients with comparison of insulin versus non-insulin therapy in the diabetic patients

The effect of insulin therapy on adverse cardiovascular outcomes in diabetic patients has been debated and a reduced benefit in clinical restenosis outcomes after sirolimus stenting has been reported among diabetic patients requiring insulin therapy. We analyzed 297 diabetic patients receiving sirolimus-eluting stents, including 115 (39%) on insulin therapy, and compared outcomes with 541 nondiabetic patients treated consecutively during the same interval. The rates of target lesion revascularization (9.5% vs 3.5%, p = 0.003) and cardiac death or myocardial infarction (MI, 7.1% vs 3.1%, p = 0.012) were significantly higher for diabetic patients. Insulin treatment was independently associated with increased risk for target lesion revascularization (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.22 to 5.00) and cardiac death or MI (hazard ratio [HR] 2.85, 95% CI 1.41 to 5.77), whereas the adjusted risk for diabetic patients not treated with insulin was not significantly different from patients without diabetes for target lesion revascularization (OR 1.32, 95% CI 0.66 to 2.62) or cardiac death or MI (HR 1.04, 95% CI 0.50 to 2.17). In conclusion, diabetes mellitus is associated with increased risk for target lesion revascularization and cardiac death or MI after receiving sirolimus-eluting stenting, and is significantly exaggerated by the requirement for insulin therapy.     

Chronic renal failure in non-insulin-dependent diabetes mellitus. A population-based study in Rochester, Minnesota

STUDY OBJECTIVE: To identify the incidence of clinically defined chronic renal failure by clinical type of diabetes in a community diabetic incidence cohort, and to evaluate the relation between persistent proteinuria and chronic renal failure in non-insulin-dependent diabetes mellitus. DESIGN: Retrospective incidence cohort study. SETTING: Population-based in Rochester, Minnesota. PATIENTS: Residents of Rochester, Minnesota, with diabetes initially diagnosed between 1945 and 1979 who had follow-up to 1984 for clinically defined chronic renal failure. MEASUREMENTS AND MAIN RESULTS: Among 1832 persons with non-insulin-dependent diabetes who were initially free of chronic renal failure, 25 developed chronic renal failure (incidence, 133 per 100,000 person-years: CI, 86 to 196). The subsequent incidence of chronic renal failure among 136 insulin-dependent diabetic Rochester residents, three of whom developed chronic renal failure, was 170 per 100,000 person-years (CI, 35 to 497). After adjusting for potential confounding factors, we found that the risk for chronic renal failure associated with the presence of persistent proteinuria at the time of the diagnosis of non-insulin-dependent diabetes was increased 12-fold (hazard ratio, 12.1; CI, 4.3 to 34.0). When persistent proteinuria developed after the diagnosis of non-insulin-dependent diabetes mellitus, the cumulative risk for chronic renal failure 10 years after the diagnosis of persistent proteinuria was 11%. CONCLUSIONS: These population-based data suggest that most cases of chronic renal failure in diabetes occur in persons with non-insulin-dependent diabetes. These data also identify the increased risk for chronic renal failure among persons with non-insulin-dependent diabetes mellitus who have persistent proteinuria present at or developing after the diagnosis of non-insulin-dependent diabetes mellitus, such data may be useful for directing interventions to prevent or delay the development of chronic renal failure.