Urinary Thrombin as a Marker of Glomerular Inflammation Associated with Renal Injury in Type 2 Diabetes.

Glomerular inflammation is a putative aggravation factor for type 2 diabetic nephropathy and urinary thrombin is a novel marker of glomerular inflammation. To clarify the relationship between glomerular inflammation and progression of the nephropathy, we measured urinary thrombin in 118 patients with type 2 diabetic nephropathy at different stages. To investigate the implications of urinary thrombin in the nephropathy, we compared urinary thrombin with expression of tissue factor, the trigger of blood coagulation activation, in glomeruli and with markers of renal injury (estimated glomerular filtration rate (eGFR) and proteinuria). Urinary thrombin was found in 4.9% (3/61), 0.0% (0/12), 29.6% (8/27) and 50.0% (9/18) of patient groups at stages 1, 2, 3 and 4, respectively. Thus, urinary thrombin was negligible in the patients at early stages (stages 1 and 2), but was present predominantly in the patients at advanced stages (stages 3 and 4). Tissue factor was expressed in accumulated macrophages in glomeruli, which indicates that thrombin may be generated in inflamed glomeruli presumably via inflammation-induced activation of the exudated coagulation factors into glomerular tissues and then be excreted in urine. Urinary thrombin was significantly associated with both decreased eGFR and increased proteinuria in type 2 diabetic nephropathy. Therefore, increased urinary thrombin in patients with advanced stages of type 2 diabetic nephropathy suggests that glomerular inflammation may injure the tissues, thereby impairing renal function. Monitoring an effect of anti-diabetic treatments on glomerular inflammation in the patients with type 2 diabetic nephropathy may be a possible application of urinary thrombin.

A case of fulminant type 1 diabetes with transiently positive anti-GAD antibodies.

A subtype of idiopathic type 1 diabetes with a rapid onset and no diabetes-related antibodies has been recently advocated as non-autoimmune fulminant type 1 diabetes. However, it is not definite yet that this subtype is always caused by non-autoimmune mechanism. A 48-year-old man was admitted to our hospital because of high plasma glucose and renal insufficiency. Laboratory findings were as follows: plasma glucose 1052 mg/dL, urinary ketone bodies (+/-), arterial blood pH 7.44, bicarbonate 23.8 mmol/L, base excess 0.3 mmol/L, plasma osmolality 342 mOsm/L, serum creatinine 2.1 mg/dL, blood urea nitrogen 69.7 mg/dL, and serum creatine kinase 1024 IU/L, giving a diagnosis of acute renal failure secondary to rhabdomyolysis associated with diabetes. Urinary C-peptide reactivity was 4.7 microg/day. The level of HbAlc was 7.0%, not so high as compared to that of plasma glucose, indicating an aggravation of diabetes within the recent short period. Antibodies to islet cell antigen, IA-2 and insulin were negative, while those to glutamic acid decarboxylase (GAD) were positive at 13.1 U/mL, which were negative half a year and two years and a half later. Serum amylase level was within normal range at admission, increased to 380 IU/L and normalized in 4 to 5 weeks as serum creatinine lowered. These data are compatible to the diagnosis of fulminant type 1 diabetes. However, the present case is different from others in positive antibodies to GAD at admission that turned to be negative subsequently. Considering our results and others together, further investigations are necessary to clarify whether all cases of fulminant type 1 diabetes are non-autoimmune or some of them are caused by autoimmune mechanism.