Should thyroid-stimulating hormone goals be reviewed in patients with type 1 diabetes mellitus? Results from the Brazilian Type 1 Diabetes Study Group.

AIMS: To investigate if thyroid-stimulating hormone (TSH) levels are associated with any differences in glycaemic control or diabetes-related complications in individuals with Type 1 diabetes. METHODS: This observational, cross-sectional and multicentre study included patients with Type 1 diabetes for ≥ 5 years, with a recent TSH measurement and without a known previous thyroid disease. Patients were divided into three groups according to TSH levels: 0.4-2.5 mU/l; 2.5-4.4 mU/l; and ≥ 4.5 mU/l. RESULTS: We included 1205 individuals with a mean ± sd age of 23.8 ± 11.3 years. Seven patients had TSH levels <0.4 mU/l and were excluded from the comparison between groups. HbA1c levels, systolic and diastolic blood pressure, LDL cholesterol and disease duration were similar in all groups (P = 0.893, P = 0.548, P = 0.461, P = 0.575 and P = 0.764, respectively). The rates of diabetic retinopathy and GFR < 60/mL/min/1.73 m(2) differed between groups (P = 0.006 and P < 0.001, respectively) and were lower in those with lower TSH levels. Multivariate analysis confirmed these associations. The frequencies of retinopathy and GFR < 60 mL/min/1.73 m(2) were higher not only in patients with TSH ≥ 4.5 mU/l (odds ratio 1.878 and 2.271, respectively) but also in those with TSH levels of 2.5-4.4 mU/l (odds ratio 1.493 and 2.286, respectively), when compared with patients with TSH levels of 0.4-2.5 mU/l. CONCLUSIONS: TSH levels of 0.4-2.5 mU/l are associated with a lower risk of diabetic retinopathy and renal failure in individuals with Type 1 diabetes, independently of glycaemic control and duration of the disease.

Assessment of arterial stiffness in women with gestational diabetes.

AIMS: Gestational diabetes mellitus may precede development of Type 2 diabetes and may be related to cardiovascular disease. Pulse wave velocity measurement is the gold-standard method to evaluate arterial stiffness, a preclinical cardiovascular risk marker. However, the relationship between aortic stiffness and gestational diabetes is unclear. The aim of this study was to evaluate aortic pulse wave velocity in women with gestational diabetes in comparison with a matched control group of healthy pregnant women. METHODS: This case-control study included 24 women with gestational diabetes and 27 matched control subjects. Clinical, demographic and laboratory variables were obtained and aortic pulse wave velocity were measured. RESULTS: Both groups had similar age, gestational age, BMI, ethnicity, smoking status and blood pressure levels. Women with gestational diabetes had aortic pulse wave velocity comparable with control subjects: 7.2 ± 0.9 vs. 7.3 ± 1.2 m/s (P = 0.79). When categorized according to the median value of pulse wave velocity (7.3 m/s), age (P < 0.001), diastolic blood pressure (P = 0.03) and heart rate (P = 0.02) were associated with increased arterial stiffness. In the group with gestational diabetes, there was a non-significant trend towards higher 1-h postprandial glycaemia in patients with higher (above the median) pulse wave velocity (6.5 ± 0.8 vs. 7.1 ± 1.3 mmol/l, P = 0.22) and a lower prevalence of patients with good glycaemic control (38.5 vs. 72.7%, P = 0.09). CONCLUSIONS: Although gestational diabetes may be a risk factor for development of cardiovascular disease, women with gestational diabetes do not have higher aortic stiffness than healthy pregnant women. Time of exposure to hyperglycaemia may have been insufficient to increase central arterial stiffness in women with gestational diabetes.

HbA1c variability and long-term glycemic control are linked to peripheral neuropathy in patients with type 1 diabetes.

BACKGROUND: HbA1c variability has been linked to retinopathy, renal disease and autonomic neuropathy in patients with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D). Although the same relationship has been demonstrated for diabetic peripheral neuropathy (DPN) in patients with T2D, data for T1D are still lacking. METHODS: Patients older than 17 years of age with ≥ 10 years of T1D duration and follow-up were included. All patients underwent nerve conduction studies and neurological examination. Laboratorial data was retrospectively extracted from chart review. Mean HbA1c (mHbA1c) over 10 years was calculated, as well as HbA1c variability estimated by standard deviation (HbA1c-SD) and coefficient of variation (HbA1c-CV). RESULTS: Fifty patients with T1D were included (30 females and 21 non-caucasians), with mean age and T1D duration of 25.6 ± 5.0 and 17.9 ± 6.1 years, respectively. The frequency of DPN was 24%. Higher mHbA1c (10.4 ± % vs 8.1 ± %; p < 0.001), HbA1c-SD (1.8 ± 0.8 vs 0.9 ± 0.4; p < 0.001), and HbA1c-CV (1.7 ± 0.8 vs 1.2 ± 1.1; p = 0.006) were observed in patients with DPN compared to others. SD-HbA1c and HbA1c-CV were associated with DPN, diagnosed by either clinical or NCS criteria, independent of mHbA1c, age and gender. CONCLUSIONS: Not only long-term glycemic control, but also its variability is associated with DPN in patients with T1D. Larger studies are required to confirm this finding.

The potential effect of ultra-long insulin degludec on glycemic variability.

Despite the therapeutic advances in the treatment of diabetes, metabolic control instability due to glycemic variability (GV) is frequently observed in patients with diabetes on intensive insulin therapy and is associated with hyperglycemic peaks and hypoglycemic episodes. Hyperglycemia associated with GV has been implicated in the development of chronic complications due to its pro-oxidative consequences. On the other hand, hypoglycemia can be associated with increased cardiovascular risk secondarily to adrenergic activation. The ultra-long-acting insulin analogue, insulin degludec (IDeg), presents a flat and stable glucose-lowering effect both in Type 1 and Type 2 diabetes patients. In pharmacodynamic studies, IDeg has been associated with a lower variability in its insulin action than other alternatives for basal insulin, which might have clinical advantages for the stability of the glycemic control. The main objective of this review is to present pharmacological and clinical data regarding the efficacy and safety of IDeg for the treatment of diabetes focusing on its effects on GV and on hypoglycemia frequency.

Insulin mediated improvement in glycemic control in elderly with type 2 diabetes mellitus can improve depressive symptoms and does not seem to impair health-related quality of life.

BACKGROUND AND OBJECTIVES: Type 2 diabetes (T2D) is very prevalent among the elderly. Insulin therapy is often required for glycemic control. The association of starting this therapy with depressive symptoms as well the health-related quality of life (HRQoL) is unknown among the elderly patients. AIMS: Evaluate the association of starting insulin therapy depressive symptoms as well with HRQoL of elderly people with T2D. METHODS: 36 T2D participants (67.9 % females, age 66.5 years ± 5.1) were recruited, 26 of whom completed the follow-up. Generic (Short-Form 36 Health Survey - SF-36) and specific (Problem Areas in Diabetes - PAID) HRQoL questionnaires, Beck Depression Inventory (BDI), clinical, laboratorial and socio-demographic data were recorded on baseline and 6 months after the beginning of insulin treatment. RESULTS: There was a reduction in the BDI score after the use of insulin, which means an improvement in depressive symptoms (Before/After: median - 10.5 / 7; p = 0008). There were no statistically significant differences in HRQoL scores between the two time periods There was also a reduction in HbA1c (Before/After: median - 8.7/7.9). Otherwise, there were no statistically significant differences in: BMI (28.1/28.3); Abdominal circumference:(100.5/99.5) and chronic complications status. CONCLUSION: Insulin therapy in elderly people with type 2 diabetes can lead to an improvement of depressive symptoms and does not seem to affect negatively HRQoL of the participants.

Prospective evaluation of glutamine and phospholipids levels in first degree relatives of patients with Type 1 Diabetes from a multiethnic population.

BACKGROUND: A dysregulation in the metabolism of lipids may be an early marker of autoimmunity in Type 1 Diabetes (T1D). It would be of general importance to identify metabolic patterns that would predict the risk for T1D later in life. The aim of this study was to perform a prospective evaluation of glutamine and phospholipids levels in Brazilian first degree relatives (FDR) of patients with T1D in a mean interval of 5 years. FINDINGS: Brazilian FDR (n = 30) of patients with T1D were evaluated and blood was sampled to measure the levels of glutamine and phospholipids in the fasting serum by quantitative colorimetric method. The tests were repeated after a mean interval of 5 years and compared to a control group (n = 20). The FDR presented lower levels of phospholipids than controls (p = 0.028), but not of glutamine (p = 0.075). Phospholipids levels decreased over time (p = 0.028) in FDR and were associated with Glutamic acid decarboxylase autoantibody (GADA) titers (p = 0.045), autoantibody positivity (p = 0.008) and PTPN22 polymorphisms (p = 0.014). CONCLUSIONS: In this Brazilian multiethnic population, there was a significant decrease in phospholipids levels in FDR in patients with T1D during a 5-year prospective follow-up, as well as a significant association between these metabolite, GADA and PTPN22 polymorphisms. For Glutamine no difference was found. These findings suggest that a dysregulation in the metabolism of lipids may precede the onset of the autoimmunity in T1D.

Relationship between the prevalence of anti-glutamic acid decarboxylase autoantibodies and duration of type 1 diabetes mellitus in Brazilian patients.

The objective of the present study was to determine whether the duration of disease has any influence on the prevalence of glutamic acid decarboxylase autoantibodies (GADA) in Brazilian patients with type 1 diabetes (T1D) and variable disease duration. We evaluated 83 patients with T1D. All participants were interviewed and blood was obtained for GADA measurement by a commercial radioimmunoassay (RSR Limited, Cardiff, UK). Four groups of patients were established according to disease duration: A) 1-5 years of disease (N = 24), B) 6-10 years of disease (N = 19), C) 11-15 years of disease (N = 25), and D) >15 years of disease (N = 15). GADA prevalence and its titers were determined in each group. GADA was positive in 38 patients (45.8%) and its frequency did not differ between the groups. The prevalence was 11/24 (45.8%), 8/19 (42.1%), 13/25 (52%), and 6/15 (40%) in groups A, B, C, and D, respectively (P = 0.874). Mean GADA titer was 12.54 +/- 11.33 U/ml for the sample as a whole and 11.95 +/- 11.8, 12.85 +/- 12.07, 10.57 +/- 8.35, and 17.45 +/- 16.1 U/ml for groups A, B, C, and D, respectively (P = 0.686). Sex, age at diagnosis or ethnic background had no significant effect on GADA (+) frequency. In conclusion, in this transversal study, duration of disease did not affect significantly the prevalence of GADA or its titers in patients with T1D after one year of diagnosis. This was the first study to report this finding in the Brazilian population.

Pancreatic autoantibodies, HLA DR and PTPN22 polymorphisms in first degree relatives of patients with type 1 diabetes and multiethnic background.

AIM: To evaluate the prevalence of pancreatic auto-antibodies (PAb) as well as its relationship with HLA DR B1 and PTPN22 polymorphisms in first degree relatives (FDR) of Brazilian patients with Type 1 diabetes (T1D) and multiethnic background. METHODS: FDR of patients with T1D were interviewed and blood was sampled for PAb measurement, HLA DRB1 and PTPN22 genotyping. Genotyping was also performed in index cases. RESULTS: In FDR (n=78), 16.7% presented at least one PAb. These individuals had a higher prevalence of HLA DRB1* 03 than others (p=0.03), without differences in PTPN22 genotyping. While the genetic profile was similar in FDR with PAb and their index cases, those without PAb had a lower frequency of HLA DR B1 * 03 than their correspondent patients (p=0.009). CONCLUSION: In this multiethnic population, a significant proportion of FDR of T1D patients had PAb, which was associated with HLA DR B1 * 03 but not with the PTPN22 polymorphism.

Family history of type 2 diabetes is increased in patients with type 1 diabetes.

It has been suggested that type 1 (T1D) and type 2 diabetes (T2D) might share some susceptibility risk factors. A higher prevalence of T2D has been reported in families of Caucasian T1D children than in the general population, although data in adults and multiethnic groups is still lacking. Our goal was to compare the prevalence of T2D family history between adults with T1D from a multiethnic population and a non-diabetic control group. We performed a cross-sectional analysis of 145 adults with T1D and 141 healthy adults (control group) that included an interview and a review of the medical charts. Groups were matched for age, sex, ethnicity and body mass index (BMI). We found a higher prevalence of not only T1D but also T2D in first-degree relatives of patients than in controls (p<0.001 and p=0.042, respectively). These differences were not observed for second/third-degree relatives. When subjects were stratified according to their ethnicity, the higher frequency of T2D in FDR of patients than controls became more striking in non-white (p=0.002) and disappeared in white individuals (p=0.85). To conclude, the prevalence of T1D and T2D was higher in first-degree relatives of patients with T1D than of controls. The difference in T2D family history between patients and controls was specially striking among non-whites, which may represent a peculiarity of T1D in this group.

Relationship between the prevalence of anti-glutamic acid decarboxylase autoantibodies and duration of type 1 diabetes mellitus in Brazilian patients

The objective of the present study was to determine whether the duration of disease has any influence on the prevalence of glutamic acid decarboxylase autoantibodies (GADA) in Brazilian patients with type 1 diabetes (T1D) and variable disease duration. We evaluated 83 patients with T1D. All participants were interviewed and blood was obtained for GADA measurement by a commercial radioimmunoassay (RSR Limited, Cardiff, UK). Four groups of patients were established according to disease duration: A) 1-5 years of disease (N = 24), B) 6-10 years of disease (N = 19), C) 11-15 years of disease (N = 25), and D) >15 years of disease (N = 15). GADA prevalence and its titers were determined in each group. GADA was positive in 38 patients (45.8 percent) and its frequency did not differ between the groups. The prevalence was 11/24 (45.8 percent), 8/19 (42.1 percent), 13/25 (52 percent), and 6/15 (40 percent) in groups A, B, C, and D, respectively (P = 0.874). Mean GADA titer was 12.54 ± 11.33 U/ml for the sample as a whole and 11.95 ± 11.8, 12.85 ± 12.07, 10.57 ± 8.35, and 17.45 ± 16.1 U/ml for groups A, B, C, and D, respectively (P = 0.686). Sex, age at diagnosis or ethnic background had no significant effect on GADA (+) frequency. In conclusion, in this transversal study, duration of disease did not affect significantly the prevalence of GADA or its titers in patients with T1D after one year of diagnosis. This was the first study to report this finding in the Brazilian population.