Adolpho Milech

Diabetic ketoacidosis in adults: update of an old complication

Diabetic ketoacidosis is an acute complication of Diabetes Mellitus characterized by hyperglycemia, metabolic acidosis, dehydration, and ketosis, in patients with profound insulin deficiency. It occurs predominantly in patients with type 1 diabetes and is frequently precipitated by infections, insulin withdrawal or undiagnosed type 1 diabetes. The authors review its pathophysiology, diagnostic criteria and treatment options in adults, as well as its complications.

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.

C-peptide residual secretion makes difference on type 1 diabetes management?

Type 1 diabetes is a chronic disease characterized by progressive destruction of the pancreatic beta cells, what leads to insulin deficiency and hyperglycemia. However, a significant secretory function may persist for long periods in a few patients, what is clinically evident through the detection of serum C peptide. This phenomenon might reduce the risk of chronic complications, severe hypoglycemias and allow easier metabolic control. It is possible that these advantages are caused, at least partially, by C peptide itself, acting directly in its target tissues.

Low triglyceride levels are associated with a better metabolic control in patients with type 1 diabetes

BackgroundAlthough it is well known in the literature that high triglyceride serum (TG) levels can jeopardize the metabolic control, little is known about the influence of low TG on type 1 diabetes patients (T1D). The aim of this study is to investigate the distribution of TG serum levels in individuals with T1D and its relationship with metabolic control.FindingsWe reviewed the medical charts of 180 patients with T1D, who were classified in groups according to TG levels: 1) low (below 50 mg/dL); 2) normal (50-150 mg/dL); 3) high (above 150 mg/dL). TG were low in 21.1% (n = 38; group 1), normal in 68.6% (n = 123; group 2) and high in 10.6% (n = 19; group 3). High TG was associated with a poor metabolic control (p < 0.001). Patients with TG lower than 50 mg/dL had a lower HbA1c than those with TG between 50 and 150 mg/dL (7.41+/-1.50% vs 8.56%+/-1.94%; p = 0.002).ConclusionTG lower than 50 mg/dL was common and might be associated with a better metabolic control in patients with T1D, although it is not clear whether the former is the cause or consequence for the latter.

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.

Relato de caso: diabetes Flatbush - da cetoacidose ao tratamento não-farmacológico

A subgroup of patients presents diabetic ketoacidosis at the onset of diabetes mellitus (DM) but later is classified as type 2 DM based on the clinical follow-up. These individuals, most commonly obese of African or Hispanic origin, have negative auto-antibodies associated with type 1 DM, but frequently HLA class II DRB1*03 and/or DRB1*04 are detected. This peculiar subtype of DM is commonly referred to as diabetes flatbush. Here we report the case of a Caucasian patient that exhibited the described evolution and in whom it was possible to withdraw insulin therapy. The possible factors associated with this favorable development are also discussed.

Avaliação da função pancreática em pacientes com diabetes melito tipo 1 de acordo com a duração da doença

Patients with type 1 diabetes (T1D) may exhibit some residual insulin secretion for many years after their diagnosis. This has been associated with a more favorable prognosis. OBJECTIVE: To analyze insulin secretion in individuals with T1D using C-peptide (CP) response to glucagon and comparing patients with recent onset ( 5 years -Group 2). METHODS: Subjects with T1D had their blood sampled before (fasting) and 6 minutes after glucagon infusion for CP, HbA1c and anti-GAD measurement. RESULTS: Forty-three individuals were evaluated, 22 in Group 1 and 21 in Group 2. Preserved insulin secretion (CP >1.5 ng/mL) was observed in 6 (13.9%) and in 8 (18.6%) patients before (CP 1) and after (CP 2) glucagon stimulus, respectively, showing no difference between the groups (p=0.18 and 0.24). CP 1 and CP 2 were detectable (>0.5 ng/dL) in 13 (30.2%) and 18 (41.9%) patients, respectively. Both were more frequent in Group 1 than in Group 2 (p=0.45 for CP1/p=0.001 for CP 2). Similar serum levels where seen between the groups, both before and after stimulus (1.4±0.8 vs. 1.2±1.0; p=0.69 and 1.8±1.5 vs. 1.7±0.8; p=0.91). Group 1 presented an inverse correlation between disease duration and CP 2 (R=-0.58; p=0.025). CONCLUSION: A significant number of patients with T1D have detectable residual insulin secretion, especially in the first 5 years of disease. These subjects are an ideal population for clinical trials that target the prevention of β cell function loss in T1D.

Zinc transporter 8 autoantibodies in patients with type 1 diabetes from a multiethnic population and their first degree relatives

OBJECTIVE Zinc transporter 8 autoantibodies (ZnT8A) have been poorly studied in non-Caucasian individuals. We aimed to investigate the prevalence of ZnT8 autoantibodies in patients with T1D and their first degree relatives (FDR) from a multiethnic population, as well as its relation with the insulin (INS) or the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene polymorphisms. SUBJECTS AND METHODS ZnT8A were analyzed in sera from T1D patients (n = 72, mean age of 30.3 ± 11.4 years) of variable duration (15.7 ± 11.8 years) and their FDR (n = 78, mean age of 18.3 ± 9.1 years) by a triple mix Radioligand Binding Assay (RBA) for the ZnT8 autoantibody (ZnT8-RWQ) variants. SNP (single nucleotide polymorphism) for INS and PTPN22 were genotyped. RESULTS The prevalence of ZnT8A was higher in T1D patients than FDR, for ZnT8TripleA (24% vs. 4%,p = 0.001), ZnT8RA (24% vs. 4%, p < 0.001) and ZnT8QA (15% vs. 3%, p = 0.004). All FDR with ZnT8A (n = 3) had at least another positive antibody. Heterozygosis for PTPN22 was associated with a higher frequency of ZnT8TripleA (p = 0.039) and ZnT8RA (p = 0.038). CONCLUSIONS ZnT8A is observed in non-Caucasian patients with T1D, even years after the disease onset, as well as in their FDR. In those, there was an overlap between ZnT8A and other T1D antibodies. ZnT8A was associated with PTPN22 polymorphisms. Further longitudinal studies are necessary to elucidate the importance of these findings in the natural history of T1D patients with multiethnic background.

Implicações clínicas da persistência de anti-GAD positivo e peptídeo C detectável em pacientes com diabetes melito tipo 1 de longa duração

OBJETIVO: Avaliar se anti-GAD positivo e PC detectavel se correlacionam com a presenca de outras doencas autoimunes, com controle glicemico e com risco de retinopatia no diabetes melito tipo 1 (DMT1) > 3 anos de duracao. PACIENTES E METODOS: Cinquenta sujeitos com DMT1 foram entrevistados, realizaram fundoscopia e dosaram PC pre e pos-glucagon, HbA1C e anti-GAD. RESULTADOS: Pacientes anti-GAD+ (n = 17) apresentaram maior frequencia de doencas autoimunes em relacao aos demais (p = 0,02). PC detectavel (n = 11) tambem foi associado ao aumento dessa prevalencia (p = 0,03), porem nenhum dos dois parâmetros influenciou na presenca de retinopatia diabetica. PC detectavel nao influenciou no controle glicemico (HbA1C media) (p = 0,28), porem as doses diarias de insulina foram mais baixas (0,62 vs. 0,91 U/kg/dia; p = 0,004) neste grupo. CONCLUSAO: Apesar de nao ser um marcador para outras doencas autoimunes, o anti-GAD+ parece ser nao so um sinalizador de autoimunidade pancreatica. PC detectavel tambem parece ter papel promissor na deteccao dessas comorbidades. Ambos nao interferiram na presenca de retinopatia, entretanto, o PC detectavel se relacionou a menores necessidades de insulina.

Revisão da hiperglicemia pós-prandial e a hipoglicemia no controle do diabetes mellitus: o papel da insulina lispro e suas pré-misturas nos picos e vales

Correction of post-prandial hyperglycemia is increasingly becoming important to patients with diabetes type 1 (DM1) and type 2 (DM2) in order to reduce their risk of morbidity and mortality. Epidemiological studies have indicated that there is a strong relationship between the degree of glycemic control, determined by HbA1c levels, and the frequency of cardiovascular events and mortality. Acute hyperglycemia has been implicated as a contributed factor for increasing the incidence of myocardial infarction, cardiac mortality and in the genesis of the microangiopathic complications. Intensive treatment, usually involving multiple insulin injections, and tight glucose control have been suggested by trials as DCCT, Kumamoto and UKPDS as the ideal treatment in patients with DM in order to prevent chronic diabetic complications. However, intensive treatment may lead to an increased incidence of hypoglycemic episodes, including severe hypoglycemia, which can be a limiting factor for achievement of optimal metabolic control. Ideal agents to treat DM should improve the postprandial and global glycemic control with no increased or less risk of hypoglycemia. We revise the clinical profile of a rapid-acting human insulin analogue, insulin lispro, and of a new long-acting analog insulin lispro NPL and fixed mixtures of insulin lispro and NPL (insulin lispro Mix25 and insulin lispro Mix50). Lispro mixtures, like insulin lispro itself, reduce the postprandial glucose rise compared to human insulin NPH or mixtures of similar ratios with equivalent doses of the insulin. Additionally insulin lispro, lispro Mix25 and Mix50 decrease the risk of hypoglycemia associated with human insulin preparations, particularly nocturnal episodes. Insulin lispro Mix25 may be a good therapy for DM1 or DM2 who are currently taking a similar ratio of short- to intermediate-acting insulin, using NPH alone, or experiencing inadequate control on oral antidiabetic agents.