Double-diabetes in a real-world sample of 2711 individuals: associated with insulin treatment or part of the heterogeneity of type 1 diabetes?

BACKGROUND: Double diabetes (DD) describes both individuals with obesity upon diagnosis of type 1 diabetes and those who have gained weight during follow-up, although cardiovascular risk factors (CVRF) are not well understood in this group. We aim to evaluate the frequency of DD in a real-world type 1 diabetes sample and the interaction of insulin treatment with CVRF. METHODS: Multicentre cross-sectional study of 2711 individuals with clinical diagnosis of type 1 diabetes from secondary diabetes centres in 20 Brazilian cities. RESULTS: Patients with diabetes duration <5 and ≥5 years had similar frequency of overweight (20.4 vs. 25 %) and obesity, (9.8 vs. 6.1 %), p 0.28 for trend. Insulin dose (U/kg/day) was lower in obese individuals compared to normal BMI, with mean (95 % CI) 0.72 (0.62-0.83) vs. 0.88 (0.84-0.92) U/kg/day for diabetes duration <5 years and 0.84 (0.77-0.92) vs. 0.99 (0.97-1.01) U/kg/day for duration ≥5 years. Obese individuals had lower HDL (47.5 vs. 54.4 mg/dL) and higher non-HDL-cholesterol (134.5 vs. 115.2 mg/dL) than lean ones only among those with more than 5 years of diabetes. CONCLUSIONS: Lower insulin doses in obese individuals point to a role of clinical heterogeneity in insulin deficiency rather than normal progression of type 1 diabetes. Early obesity in type 1 diabetes is associated to lower HDL-cholesterol and higher number of CVRF. These data suggest a broad landscape of pathophysiological phenomena in double diabetes, rather than simple progression of a homogeneous clinical entity.

Economic status and clinical care in young type 1 diabetes patients: a nationwide multicenter study in Brazil.

The aim of this study is to evaluate the influence of economic status on clinical care provided to Brazilian youths with type 1 diabetes in daily practice, according to the American Diabetes Association's guidelines. This was a cross-sectional, multicenter study conducted between 2008 and 2010 in 28 public clinics in Brazil. Data were obtained from 1,692 patients (55.3 % female, 56.4 % Caucasian), with a mean age of 13 years (range, 1-18), a mean age at diagnosis of 7.1 ± 4 years and diabetes duration of 5 ± 3.7 years. Overall, 75 % of the patients were of a low or very low economic status. HbA1c goals were reached by 23.2 %, LDL cholesterol by 57.9 %, systolic blood pressure by 83.9 % and diastolic blood pressure by 73.9 % of the patients. In total, 20.2 % of the patients were overweight and 9.2 % were obese. Patients from very low economic status were less likely to attend tertiary care level when compared with those from low, medium and high economic status, 64.2 % versus 75.5 % versus 78.3 % and 74.0 %; p < 0.001, respectively. The rate of annual screening for retinopathy, nephropathy and for foot alterations was 66.2, 69.7 and 62.7 %, respectively. Insulin dose, age, very low economic status, daily frequency of self-blood glucose monitoring and female gender were independently associated with poor glycemic control. Screening for diabetic complications and attaining glucose, lipid and blood pressure goals present a challenge for young Brazilian type 1 diabetes patients. The low economic status of the majority of our patients may represent a barrier to reaching these goals.

Heterogeneous behavior of lipids according to HbA1c levels undermines the plausibility of metabolic syndrome in type 1 diabetes: data from a nationwide multicenter survey.

BACKGROUND: Cardiovascular risk factors (CVRF) may cluster in type 1 diabetes, analogously to the metabolic syndrome described in type 2 diabetes. The threshold of HbA1c above which lipid variables start changing behavior is unclear. This study aims to 1) assess the behavior of dyslipidemia according to HbA1c values; 2) detect a threshold of HbA1c beyond which lipids start to change and 3) compare the clustering of lipids and other non-lipid CVRF among strata of HbA1c individuals with type 1 diabetes. METHODS: Effects of HbA1c quintiles (1st: ≤7.4%; 2nd: 7.5-8.5%; 3rd: 8.6-9.6%; 4th: 9.7-11.3%; and 5th: >11.5%) and covariates (gender, BMI, blood pressure, insulin daily dose, lipids, statin use, diabetes duration) on dyslipidemia were studied in 1275 individuals from the Brazilian multi-centre type 1 diabetes study and 171 normal controls. RESULTS: Body size and blood pressure were not correlated to lipids and glycemic control. OR (99% CI) for high-LDL were 2.07 (1.21-3.54) and 2.51 (1.46-4.31), in the 4th and 5th HbA1c quintiles, respectively. Hypertriglyceridemia increased in the 5th quintile of HbA1c, OR 2.76 (1.20-6.37). OR of low-HDL-cholesterol were 0.48 (0.24-0.98) and 0.41 (0.19-0.85) in the 3rd and 4th HbA1c quintiles, respectively. HDL-cholesterol correlated positively (0.437) with HbA1c in the 3rd quintile. HDL-cholesterol and insulin dose correlated inversely in all levels of glycemic control. CONCLUSIONS: Correlation of serum lipids with HbA1c is heterogeneous across the spectrum of glycemic control in type 1 diabetes individuals. LDL-cholesterol and triglycerides worsened alongside HbA1c with distinct thresholds. Association of lower HDL-cholesterol with higher daily insulin dose is consistent and it points out to a role of exogenous hyperinsulinemia in the pathophysiology of the CVRF clustering. These data suggest diverse pathophysiological processes depending on HbA1c, refuting a unified explanation for cardiovascular risk in type 1 diabetes.

Regional differences in clinical care among patients with type 1 diabetes in Brazil: Brazilian Type 1 Diabetes Study Group.

BACKGROUND: To determine the characteristics of clinical care offered to type 1 diabetic patients across the four distinct regions of Brazil, with geographic and contrasting socioeconomic differences. Glycemic control, prevalence of cardiovascular risk factors, screening for chronic complications and the frequency that the recommended treatment goals were met using the American Diabetes Association guidelines were evaluated. METHODS: This was a cross-sectional, multicenter study conducted from December 2008 to December 2010 in 28 secondary and tertiary care public clinics in 20 Brazilian cities in north/northeast, mid-west, southeast and south regions. The data were obtained from 3,591 patients (56.0% females and 57.1% Caucasians) aged 21.2 ± 11.7 years with a disease duration of 9.6 ± 8.1 years (<1 to 50 years). RESULTS: Overall, 18.4% patients had HbA1c levels <7.0%, and 47.5% patients had HbA1c levels ≥ 9%. HbA1c levels were associated with lower economic status, female gender, age and the daily frequency of self-blood glucose monitoring (SBGM) but not with insulin regimen and geographic region. Hypertension was more frequent in the mid-west (32%) and north/northeast (25%) than in the southeast (19%) and south (17%) regions (p<0.001). More patients from the southeast region achieved LDL cholesterol goals and were treated with statins (p<0.001). Fewer patients from the north/northeast and mid-west regions were screened for retinopathy and nephropathy, compared with patients from the south and southeast. Patients from the south/southeast regions had more intensive insulin regimens than patients from the north/northeast and mid-west regions (p<0.001). The most common insulin therapy combination was intermediate-acting with regular human insulin, mainly in the north/northeast region (p<0.001). The combination of insulin glargine with lispro and glulisine was more frequently used in the mid-west region (p<0.001). Patients from the north/northeast region were younger, non-Caucasian, from lower economic status, used less continuous subcutaneous insulin infusion, performed less SBGM and were less overweight/obese (p<0.001). CONCLUSIONS: A majority of patients, mainly in the north/northeast and mid-west regions, did not meet metabolic control goals and were not screened for diabetes-related chronic complications. These results should guide governmental health policy decisions, specific to each geographic region, to improve diabetes care and decrease the negative impact diabetes has on the public health system.

Prevalence of adults with type 1 diabetes who meet the goals of care in daily clinical practice: a nationwide multicenter study in Brazil.

OBJECTIVE: To determine the prevalence of patients with type 1 diabetes mellitus who meet the glycemic and cardiovascular (CV) risk factors goals and the frequency of screening for diabetic complications in Brazil according to the American Diabetes Association guidelines. RESEARCH DESIGN AND METHODS: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 1774 adult patients (56.8% females, 57.2% Caucasians) aged 30.3 ± 9.8 years with diabetes duration of 14.3 ± 8.8 years. RESULTS: Systolic blood pressure was at goal in 40.3% and diastolic blood pressure was at goal in 26.6% of hypertensive patients. LDL cholesterol and HbA1c were at the goal in 45.2% and 13.2% of the patients, respectively. Overweight was presented in 25.6% and obesity in 6.9%. Among those with more than 5 years of disease, screening for retinopathy was performed in the preceding year in 70.1%. Nephropathy and feet complications were screened in 63.1% and 65.1%, respectively. CONCLUSIONS: The majority of patients did not meet metabolic control goals and a substantial proportion was not screened for diabetic complications. These issues may increase the risk of chronic complications and negatively impact public health.

Progression to microalbuminuria in patients with type 1 diabetes: a seven-year prospective study.

BACKGROUND: The presence of microalbuminuria can be associated with overt nephropathy and cardiovascular disease in patients with type 1 diabetes (T1D). We aimed to determine the incidence and evaluate the baseline predictors for the development of microalbuminuria in patients with T1D. METHODS: This study is a longitudinal cohort study of 122 normoalbuminuric patients with T1D who were receiving routine clinical care at baseline. A detailed medical history was taken, and a physical examination was performed at baseline. All of the patients were regularly examined for diabetes-associated complications. An analysis of predictors was performed using the Cox regression. RESULTS: Over 6.81 (3.59-9.75) years of follow-up, 50 (41%) of the patients developed microalbuminuria. The incidence density was 6.79/100 people per year (95% CI 5.04-8.95), and the microalbuminuria developed after 5.9 (2.44-7.76) and 11 (5-15) years of follow-up and diabetes duration, respectively. After an individual Cox regression, the baseline variables associated with the development of microalbuminuria were age, age at diagnosis, duration of diabetes, systolic and diastolic blood pressure, fasting glycemia, body mass index (BMI), total cholesterol and triglycerides levels, cholesterol/HDL ratio and a family history of type 2 diabetes.After a multivariate Cox regression, the only independent factors associated with the development of microalbuminuria were BMI [HR 1.12 (1.03-1.21)] and cholesterol/HDL ratio [HR 1.32 (1.05-1.67)]. CONCLUSIONS: A higher BMI and cholesterol/HDL ratio increased the risk of developing microalbuminuria in young patients with T1D after a short follow-up. Both risk factors are modifiable and should be identified early and followed closely.

Effect of the carbohydrate counting method on glycemic control in patients with type 1 diabetes.

BACKGROUND: The importance of achieving and maintaining an appropriate metabolic control in patients with type 1 diabetes mellitus (DM1) has been established in many studies aiming to prevent the development of chronic complications. The carbohydrate counting method can be recommended as an additional tool in the nutritional treatment of diabetes, allowing patients with DM1 to have more flexible food choices. This study aimed to evaluate the influence of nutrition intervention and the use of multiple short-acting insulin according to the carbohydrate counting method on clinical and metabolic control in patients with DM1. METHODS: Our sample consisted of 51 patients with DM1, 32 females, aged 25.3 +/- 1.55 years. A protocol of nutritional status evaluation was applied and laboratory analysis was performed at baseline and after a three-month intervention. After the analysis of the food records, a balanced diet was prescribed using the carbohydrate counting method, and short-acting insulin was prescribed based on the total amount of carbohydrate per meal (1 unit per 15 g of carbohydrate). RESULTS: A significant decrease in A1c levels was observed from baseline to the three-month evaluation after the intervention (10.40 +/- 0.33% and 9.52 +/- 0.32%, respectively, p = 0.000). It was observed an increase in daily insulin dose after the intervention (0.99 +/- 0.65 IU/Kg and 1.05 +/- 0.05 IU/Kg, respectively, p = 0.003). No significant differences were found regarding anthropometric evaluation (BMI, waist, hip or abdominal circumferences and waist to hip ratio) after the intervention period. CONCLUSIONS: The use of short-acting insulin based on the carbohydrate counting method after a short period of time resulted in a significant improvement of the glycemic control in patients with DM1 with no changes in body weight despite increases in the total daily insulin doses.

Assessment of cognitive status in patients with type 2 diabetes through the Mini-Mental Status Examination: a cross-sectional study.

BACKGROUND: Diabetes is considered an independent risk factor for cognitive impairment and some studies observed through neuropsychological tests that cognitive disfunction affects both elderly and younger patients with diabetes. The aims of this study were to evaluate the cognitive status of outpatients with type 2 diabetes and to evaluate factors associated with impaired function. METHODS: A cross-sectional study was conducted in a group of type 2 diabetic outpatients. They were asked to undergo the Mini-Mental State Examination (MMSE) during routine ambulatory visits between April 2006 and January 2007, with the highest pontuation of the test being 30 points. Patients were classified as having possible dementia according to years of study. Exclusion criteria were blindness, illiteracy, stroke, Alzheimer disease and psychiatric disorder. Results are presented as median (interquartile range) or mean +/- SD. RESULTS: The study group was composed of 346 type 2 diabetic outpatients (216 females), aged 58,6 +/- 12,1 years and with duration of diabetes of 12,3 +/- 9,1 years. Hypertension was present in 77,2%. The total MMSE score achieved was 26 points (16 - 30) and was correlated with years of study (R2 = 0,39, p < 0,001) and 'per capita' income (R2 = 0,22, p < 0,0001) and duration of diabetes (R2 = - 0,13, p = 0,01). Patients who needed help to take their medications obtained worst performance in the MMSE (23,16 +/- 3,55 vs 25,7 +/- 2,84, p < 0,01) and were more likely to present possible dementia (p < 0,01). Forty two subjects (12.1%) had diagnosis of possible dementia and this was also associated with years of study (p = 0,045). No association was observed between possible dementia and total MMSE scores with A1C levels. CONCLUSIONS: We conclude that patients with type 2 diabetes should be regularly evaluated for their cognitive function, because duration of disease could be associated with decline in cognition. The early implementation of mini mental which is a simple method of execution can be done to detect early stages of dementia. This test could be an important tool to access the ability of patient to understand their disease and treatment.

Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus.

AIMS: To determine prospectively the efficacy, tolerability and patient satisfaction of an extended release formulation of metformin (metformin XR) in hospital based outpatients with type 2 diabetes mellitus currently treated with standard metformin. METHODS: Patients on immediate release standard metformin either alone or combined with other oral agents were switched to extended release metformin XR 500 mg tablets and titrated to a maximum dose of 2000 mg/day Measurements to include glucose and lipid control, blood pressure, body weight, waist circumference, C-reactive protein, adverse events and patient satisfaction were recorded at baseline, three and six months. RESULTS: Complete data were obtained for 35 of the 61 patients enrolled to the study. At three and six months no changes were reported for any of the cardiovascular risk factors except for lipids where there was a modest rise in plasma triglycerides. These effects were achieved with a reduced dose of metformin XR compared to pre-study dosing with standard metformin (1500 mg +/- 402 vs 1861 +/- 711 p = 0.004). A total of 77% of patients were free of gastrointestinal side effects and 83% of patients stated a preference for metformin XR at the end of the study. Ghost tablets were reported in the faeces by the majority of the patients (54.1%). CONCLUSIONS: Patients switched to extended release metformin XR derived the same clinical and metabolic benefits as for standard metformin but with reduced dosage, fewer gastrointestinal side effects and a greater sense of well being and satisfaction on medication.

Allergic reaction related to ramipril use: a case report.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are widely prescribed for patients with diabetes as a nephroprotector drug or to treat hypertension. Generally they are safe for clinical practice, but the relationship between these drugs and angioedema is known. The exact mechanism for ACE inhibitors-induced angioedema is not clear and it is still a matter of discussion. CASE REPORT: We reported a case of a 23-year-old black female with an 11 year history of type 1 diabetes, regularly monitored in the department of diabetes, in use of 0,98 UI/kg/day of human insulin, which presented an allergic reaction 24 h after ramipril use. The drug had been prescribed to treat diabetic nephropathy. There was no previous history of drug induced or alimentary allergy. The patient was instructed to discontinue the use of ramipril and oral antihistaminic drug and topical corticosteroid were prescribed. Skin biopsies were performed and confirmed the clinical hypothesis of pharmacodermy. The evaluation of ACE polymorphism identified DD genotype. Six months after the withdrawal of ramipril the patient was prescribed the angiotensin-II receptor blocker (ARB) losartan as nephroprotector. She remained well without adverse reactions. CONCLUSIONS: ACE inhibitors-induced angioedema is uncommon and the clinical presentation is variable with lips, tongue, oropharinge, and larynge as the most common locations. The presence of angioedema during treatment requires the immediate cessation of treatment due to the risk of possible severe complications. The case reported presented moderate symptoms, with the development of early onset edema in uncommon regions. ACE DD genotype had been associated with angioedema-ACE inhibitors induced. In patients who have experienced ACE inhibitor-related angioedema, ARB should be used cautiously used. However in the case of our patient, the prescription of losartan as nefroprotector did not result in any recurrent adverse effect.

Post-transplant diabetes mellitus.

In recent decades, Diabetes Mellitus has become a severe and growing global public healthcare problem due to the increase of its prevalence, morbidity and mortality. Post-transplant diabetes mellitus (PTDM) is a complication which takes place after a solid organ transplant, and its incidence is widely variable, ranging from 2 to 53%. Some factors increase the risk of PTDM, such as age, ethnicity, cadaver-donor kidney presence of the hepatitis C virus and cytomegalovirus, overweight and obesity and the Immunosuppression scheme established in the immediate post-transplant period. High doses of tacrolimus and corticosteroid represent the highest risk for developing PTDM.Considering that the development of PTDM is associated with a higher risk of complications, such as infections and cardiovascular disease - thus representing a higher life threatening risk and a higher cost for the Health System - the relevance of identifying the risk factors and of the early diagnosis combined with appropriate therapy will be high for the follow up, and eventually resulting in the success of the procedure as far as patient survival and transplantation durability.