Adult ; Diabetes Mellitus, Type 1 ; classification ; immunology ; Diabetes Mellitus, Type 2 ; classification ; immunology ; Humans

The importance of innate immunity in host defense is becoming clear after discovery of innate immune receptors such as Toll-like receptor or Nod-like receptor. Innate immune system plays an important role in diverse pathological situations such as autoimmune diseases. Role of innate immunity in the pathogenesis of metabolic disorders such as type 2 diabetes, metabolic syndrome or atherosclerosis that has not been previously considered as inflammatory disorders, is also being appreciated. Here, the role of innate immunity in the development of type 1 diabetes, a classical organ-specific autoimmune disease, and type 2 diabetes will be discussed, focusing on the role of specific innate immune receptors involved in these disease processes.
Animals ; Cytokines/*immunology ; Diabetes Mellitus, Type 1/*immunology ; Diabetes Mellitus, Type 2/*immunology ; Humans ; Immunity, Innate/*immunology ; Inflammasomes/*immunology ; *Models, Immunological ; Pancreas/immunology

OBJECTIVETo investigate the prevalence of metabolic syndrome (MS) in latent autoimmune diabetes in adults (LADA) and to study the positivity of glutamic acid decarboxylase autoantibody (GADA) in diabetic patients with MS.

METHODSSera of 598 patients with an initial diagnosis of type 2 diabetes (T2DM) were screened for GADA with radioligand assay. These patients were divided into LADA and T2DM groups according to the titers of GADA to compare the prevalence of MS; the proportions of LADA in diabetic patients with and without MS were studied. We also compared the clinical characteristics of LADA patients with and without MS.

RESULTSAbout 23.7% of the LADA patients had MS. In patients with MS, the prevalence of LADA was 10.0%, of which approximately 95% had low GADA titers, that was, belonging to LADA-type 2. Compared with LADA patients with MS, LADA without MS were similar to classical type 1 diabetes and had features of low body weight, tendency to develop ketosis and impaired islet cell function.

CONCLUSIONAbout 23.7% patients with MS are found in LADA patients. The GADA levels in LADA patients with and without MS are significantly different, which may need different therapeutic strategies.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoantibodies ; immunology ; China ; epidemiology ; Diabetes Mellitus, Type 1 ; epidemiology ; immunology ; Diabetes Mellitus, Type 2 ; immunology ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; immunology ; Middle Aged ; Prevalence

OBJECTIVETo compare the clinical characteristics between type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) with different titers of glutamic acid decarboxylase autoantibody (GADA) and to define the two distinct subtypes of LADA.

METHODSSera of 750 patients with an initial diagnosis of T2DM from central south of China were screened for GADA using a radioligand assay. The distribution and frequency of GADA levels were described. Two hundred and ninety-five patients were divided into the T2DM group (n = 233) and the LADA group (n = 62) to compare the age of onset, body mass index, HbA(1c), C-peptide, hypertension, dyslipidemia and chronic diabetic complications. Furthermore, LADA patients with different GADA titers were subdivided to analyze the same indexes as the above.

RESULTSThe prevalence of LADA (defined as GADA > or = 0.05, namely GADA positive) was 9.7% in the 750 initially diagnosed type 2 diabetic patients. Compared with T2DM, LADA patients were younger at their ages of onset, had lower C-peptide and body mass index, and also had less cases with hypertension and with dyslipidemia. However, only patients with high titer of GADA had poorer beta cell functions and less diabetic complications compared to T2DM and low GADA titer of LADA patients. Patients with low GADA titer were similar to T2DM patients, except that they were prone to develop ketosis more frequently.

CONCLUSIONSTwo clinically distinct subtypes of LADA can be identified by GADA levels in patients initially-diagnosed as type 2 diabetes. Patients with high titer of GADA (GADA > or = 0.5) subsequently develop more insulin dependency, which are classified as LADA-type 1; while those with lower GADA titer (0.05 < or = GADA < 0.5) and having clinical and metabolic phenotypes of type 2 diabetes are classified as LADA-type 2.

Adult ; Aged ; Aged, 80 and over ; Autoantibodies ; analysis ; Autoimmune Diseases ; classification ; immunology ; Diabetes Mellitus, Type 1 ; classification ; immunology ; Diabetes Mellitus, Type 2 ; classification ; immunology ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Male ; Middle Aged

INTRODUCTIONWith advancement in the understanding of the pathogenesis underlying diabetes mellitus (DM), the boundary between type 1 and type 2 DM (T1DM and T2DM) does not seem to be as clear cut as previously thought. This study was designed to test the possibility of overlap between the spectra of immune-mediated DM and insulin resistance.

METHODSTo test for the possibility of overlap, we looked for autoantibodies typical of T1DM in patients with classical T2DM, and insulin resistance in patients with T1DM. Autoantibodies against islet cell antigen, glutamic acid decarboxylase-65 and insulinoma-associated antigen-2 were tested in 82 patients with T2DM and 27 patients with T1DM. The patients had been diagnosed on clinical criteria using standard laboratory techniques. Clinical parameters of diagnostic importance were noted, and homeostatic model assessment of insulin resistance (HOMA-IR) was calculated using fasting insulin and fasting blood glucose ratio.

RESULTSAutoantibodies against one or more beta cell antigens were detected in 12.19% of patients clinically diagnosed to have T2DM, and insulin resistance (HOMA-IR > 2.5) was diagnosed in 37.03% of patients with T1DM. It was not possible to identify any combination of clinical or biochemical markers that could predict autoantibody positivity in T2DM patients. T1DM patients with insulin resistance had a significantly higher body mass index than their insulin-sensitive counterparts (p = 0.02).

CONCLUSIONAutoantibodies against beta cell antigens are detectable in insulin-resistant T2DM patients, and insulin resistance may be present in relatively overweight T1DM patients. No differentiating clinical features that might predict autoantibody positivity in T2DM patients were found.

Adolescent ; Adult ; Autoantibodies ; blood ; immunology ; Biomarkers ; blood ; Blood Glucose ; analysis ; Body Mass Index ; Cross-Sectional Studies ; Diabetes Mellitus, Type 1 ; classification ; immunology ; Diabetes Mellitus, Type 2 ; classification ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Insulin Resistance ; immunology ; Male

OBJECTIVETo investigate the diagnostic value of serum islet autoantibody-glutamic acid decarboxylase antibody (GADA) and islet cell antibody (ICA) in patients with hepatogenic diabetes.

METHODSSerum GADA and ICA were measured with enzyme-linked immunosorbent assay (ELISA) in 217 patients with chronic hepatitis B (CH) or liver cirrhosis (LC). The positivity rate of GADA and ICA in different phases of CH and LC and their relations with diabetes mellitus were analyzed.

RESULTSThe positivity rate of the islet autoantibody in the circulation was 72% in CH and LC patients with diabetes mellitus and 30% in patients with normal glucose level, showing significant difference between the two patient groups (Chi2=36.620, P=0.000). CH patients with diabetes had much higher positivity rate for the antibody [52% than type 2 diabetic patients with liver dysfunction [8%, P<0.05]. The positivity rate was also much higher in CH and LC patients with lowered C peptide level [70%] than in those with normal C peptide level [40%, P<0.005].

CONCLUSIONBoth GADA and ICA have important value in the diagnosis of hepatogenic diabetes and may serve as indexed in laboratory test for distinguishing hepatogenic diabetes from type 2 diabetes.

Adult ; Autoantibodies ; blood ; Diabetes Mellitus, Type 1 ; complications ; diagnosis ; immunology ; Diabetes Mellitus, Type 2 ; complications ; diagnosis ; immunology ; Diagnosis, Differential ; Female ; Glutamate Decarboxylase ; immunology ; Hepatitis B, Chronic ; complications ; Humans ; Islets of Langerhans ; immunology ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Predictive Value of Tests

OBJECTIVETo explore the relation between the positive rates of autoantibodies against beta(1) adrenergic receptor (beta1-receptor)and (M2-receptor) with urinary albumin excretion rate (UAER) in type 2 diabetes patients with refractory hypertension.

METHODSAutoantibodies against beta(1)- and M(2)-receptor as well as autoantibodies were determined in type 2 diabetes patients with (n = 136) or without (n = 111) refractory hypertension, hypertensive patients without renal failure (n = 60) and healthy control subjects (n = 40, control) by ELISA.

RESULTSThe positive rates of the autoantibodies against beta1-receptors (44.9%) and M(2)-receptor (37.5%) in patients with type 2 diabetes with refractory hypertension were significantly higher than those in patients with type 2 diabetes without refractory hypertension (27.9% and 24.3%, respectively, all P < 0.05), in patients with hypertension without renal failure (11.7% and 15.0%, all P < 0.01) and in healthy controls (8.3% and 7.5%, all P < 0.01). In type 2 diabetes patients with refractory hypertension and renal failure (UAER > or = 200 microg/min), the positive rates of the autoantibodies against beta(1)-receptor (87.1%, 27/31) and against M(2)-receptor (67.7%, 21/31) were significantly higher than those in type 2 diabetes patients with refractory hypertension but without renal failure (UAER 20 - 199 microg /min, 46.7%, 28/60 and 41.7%, 25/60, respectively, all P < 0.05).

CONCLUSIONThe serum beta(1)- and M (2)-receptor autoantibodies are positively associated with the UAER level and suggest that these autoantibodies against beta(1) and M(2)-receptor may play important roles in the pathogenesis of the type 2 diabetes with refractory hypertension.

Aged ; Albuminuria ; etiology ; Autoantibodies ; analysis ; Diabetes Mellitus, Type 2 ; complications ; immunology ; Female ; Humans ; Hypertension ; complications ; immunology ; Male ; Middle Aged ; Receptor, Muscarinic M2 ; immunology ; Receptors, Adrenergic, beta-1 ; immunology

OBJECTIVETo investigate the relation between insulin resistance and glutamic acid decarboxylase antibody (GAD-Ab) titers in latent autoimmune diabetes in adults (LADA).

METHODSThe patients with phenotypic type 2 diabetes were screened for GAD-Ab positivity, and the 141 positive patients were divided into two subgroups according to the GAD-Ab titer, namely the high-titer group (LADA-1 subtype) and low-titer group (LADA-2 subgroup). The clinical features and insulin resistance were compared between the two groups. Insulin resistance was calculated by HOMA 2 software, and GAD-Ab and C peptide were determined with radioligand and radioimmune assay, respectively.

RESULTSCompared with low-titer LADA patients, the patients with high titers had younger age of onset, lower BMI, higher HbA1c level, and worse fasting and postprandial C peptide levels. The insulin resistance index by HOMA 2 was significantly lower in LADA-1 group than in LADA-2 group (1.6-/+1.1 vs 2.1-/+1.1, P=0.001). The HOMA2-IR index showed a negative correlation to GAD-Ab titer.

CONCLUSIONThe degree of insulin resistance is correlated to GAD-Ab titers in LADA, and low titer patients have higher insulin resistance level.

Adult ; Aged ; Autoantibodies ; blood ; Autoimmune Diseases ; diagnosis ; immunology ; Diabetes Mellitus, Type 2 ; diagnosis ; immunology ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Insulin Resistance ; Islets of Langerhans ; immunology ; physiology ; Male ; Middle Aged

OBJECTIVETo explore the relationship between the T cell subsets and glucose level and first-phase insulin secretion function in patients with type 2 diabetes mellitus (T2DM).

METHODSWe determined the oral glucose tolerance (OGTT), insulin release test(IRT), body mass index(BMI), glycohemoglobin A1c (HbA1c), T lymphocyte subsets (CD4(+),CD8(+)), and activity of natural kill(NK) cell and ⊿I(30)/⊿G(30) in 78 newly diagnosed T2DM patients, 60 impaired glucose tolerance (IGT) patients, and 60 normal controls.

RESULTSDM and IGT patients had significantly lower levels of CD4(+), CD4(+)/CD8(+)ratio, activity of NK cell, and ⊿I(30)/⊿G(30) and significantly higher levels of HbA1c and CD8(+)compared with normal controls(all P<0.05). Patients in DM group had significantly lower level of CD4(+),⊿I(30)/⊿G(30) and significantly higher levels of FBG and HbA1c compared with IGT group. There was no significant difference in terms of CD8(+), CD4(+)/CD8(+)ratio, and activity of NK cell between IGT and DM groups, whereas CD4(+) T cells were negatively correlated with FBG and HbA1c and positively with ⊿I(30)/⊿G(30) . Multiple regression stepwise analysis showed that CD4(+) was independently associated with HbA1c and ⊿I(30)/⊿G(30).

CONCLUSIONT2DM patients tends to have disorders in cellular immunity, which is correlated with blood glucose level and the insulin secretion function.

Adult ; Aged ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; immunology ; Female ; Humans ; Immunity, Cellular ; Insulin ; blood ; Male ; Middle Aged ; T-Lymphocyte Subsets ; immunology

OBJECTIVETo explore the role of the autoantibodies against M(2)-muscarinic receptor (M(2)-receptor), beta(1)-adrenergic receptor (beta(1)-receptor) in the development of diabetic with refractory hypertension.

METHODSSerum autoantibodies against M(2) and beta(1) were detected by ELISA using synthesized epitopes of the second extracellular loop of M(2) receptor (169 - 193) and beta(1) receptor (197 - 222) in healthy controls (n = 40), diabetic patients (n = 62), diabetic patients with non-refractory hypertension (n = 55) and diabetic patients with refractory hypertension (n = 81).

RESULTSThe positive rates of the autoantibodies against M(2) receptor and beta(1) receptor were similar among healthy controls (15.0% and 17. 5%), diabetes mellitus patients (17.7% and 14.5%) and diabetic patients with non-refractory hypertension (16.4% and 12.7%) but are significantly higher in diabetic patients with refractory hypertension (64.2% and 55.6%, P < 0.01 vs. other 3 groups).

CONCLUSIONThis finding suggests that autoimmune mechanisms might play a role in the pathogenesis of diabetic patients with refractory hypertension.

Adult ; Autoantibodies ; blood ; Diabetes Mellitus, Type 2 ; blood ; complications ; Female ; Humans ; Hypertension ; blood ; complications ; Male ; Middle Aged ; Receptor, Muscarinic M2 ; immunology ; Receptors, Adrenergic, beta-1 ; immunology