Albuminuria and low estimated glomerular filtration rate (eGFR) are known as risk factors for atherosclerotic cardiovascular disease. Carotid intima-media thickness (IMT) is widely used as a surrogate marker of systemic atherosclerosis. To determine the relationship between atherosclerosis and renal damage, we measured common carotid IMT, carotid plaque, eGFR, and albuminuria in 261 type 2 diabetes subjects without proteinuria. Mean IMT significantly increased with diabetic nephropathy progression defined by albuminuria (stage 1, 0.95±0.18 mm vs. stage 2, 1.08±0.20 mm; p<0.01) . Mean IMT in those with eGFR<60 ml/min/1.73 m² was greater than that in those with eGFR≥60 ml/min/1.73 m² (1.04±0.21 mm vs. 0.98±0.19 mm; p<0.05) . The carotid plaque progression rate increased significantly with diabetic nephropathy progression (stage 1, 32.4 %vs. stage 2, 65.9 %; p<0.01) , and low eGFR (39.9 %vs. 60.4 %, p<0.05) . Combination analysis showed that the IMT value was the highest in those with stage 2 diabetic nephropathy and high eGFR (1.08±0.17 mm) . Albuminuria interacts with eGFR. The plaque progression rate was highest, at 78.9 %, in those with stage 2 diabetic nephropathy and low eGFR. In multiple regression analysis, age and albuminuria related independently to IMT. In multiple logistic regression analysis, age, LDL-C level, triglyceride level, and albuminuria related independently to carotid plaque. These results suggest that carotid atherosclerosis is strongly associated with the presence of albuminuria and also interacts with low eGFR.

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We studied the association between total serum bilirubin concentration (TBC) and vascular complications in type 2 diabetes based on the TBCs of 171 subjects compared to those with and without diabetic microangiopathy (Micro) and to those with and without macroangiopathy (Macro) , i.e., cerebral infarction (CI) , coronary artery disease (CAD) , and peripheral arterial disease (PAD) . Stepwise regression analysis was used to determine the effects of various factors on TBC, considering the following factors as independent variables: gender, age, diabetic duration, HbA1c, Micro, Macro, systolic blood pressure (SBP) , lipid profile, alcohol intake, and smoking. Logistic regression analysis was used to determine the effects of these factors on Micro/Macro, considering the following factors as independent variables: TBC, gender, age, diabetic duration, HbA1c, SBP, lipid profile, and smoking. TBCs were significantly lower in those with retinopathy, nephropathy, CI, and PAD compared to those in subjects without complications. Micro and Macro were independent factors for TBC, while TBC, diabetic duration, SBP, and smoking were independent factors for Micro. TBC was the only explanatory variable for Macro. Low serum TBC could therefore be an important factor for the incidence of both Micro and Macro in type 2 diabetes.

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We evaluated 12-month changes in pancreatic β-cell function and influencing factors in Japanese subjects with type 2 diabetes (T2DM). Those who showed marked chronic hyperglycemia, who were severely obese, who had progressive hepatic or renal dysfunction, who used incretins, or who used a combination of insulin and an oral hypoglycemic agent (OHA) were excluded. The resulting 205 subjects showing good, stable glycemic control for at least 3 months were included in the final analysis. Pancreatic β-cell function was assessed by C-peptide reactivity (ΔCPR) for 6 min in glucagon tests. Clinical parameters were age, gender, diabetes duration, diabetic retinopathy, hypertension, urinary albumin excretion rate (AER), HbA1c, and serum lipids. In a cross-sectional study at the start of observation (baseline), diabetes duration correlated significantly negatively (r=0.357, P<0.001) with ΔCPR. Stepwise multiple regression analysis of clinical parameters identified diabetes duration as the main predictive independent variable at baseline of ΔCPR (F=16.951). In a 12-month longitudinal study of all subjects (n=205), ΔCPR decreased significantly (p<0.001), and when analyzed by treatment type, ΔCPR decreased significantly in the no-drug treatment group (Group D; n=39; p<0.05) and Group OHA (n=134; p<0.001), but did not change significantly in the insulin group (Group I; n=32). Subanalysis by drug type in Group OHA showed that insulin secretagogue OHAs, particularly sulfonylureas, played a strong role in decreasing ΔCPR. Our findings suggest that in Japanese subjects with T2DM, changes over the years in insulin secretion by pancreatic β-cells are influenced by both the natural history of hyperglycemic exposure and the history of treatment modalities undergone.

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A 24-year-old primigravida 161 cm tall, weighing 70 kg, and having a BMI of 27.0 before pregnancy and diagnosed with gestational diabetes mellitus (GDM) in a 75 g oral glucose tolerance test (OGTT) on day 4 of gestational week 23 (23w4d) was hospitalized on 26w5d. Ritodrine hydrochloride was administered to delay premature labor and insulin therapy was initiated 3 days later. Premature labor persisted despite maximum ritodrine dosage and the subject was transferred to our hospital on 29w0d. She was administered 12 mg of betamethasone intramuscularly on 29w0d and 29w1d. Magnesium sulfate infusion at ~2 g/hr was administered until 36w1d. Ritodrine at ~200 μg/min was continued until 37w0d. Her insulin requirement increased from 70 U/day on 29w0d to 203 U/day on 35w0d. It began decreasing after ritodrine was discontinued and decreased markedly from 178 U/day to 20 U/day. She delivered a normal male baby weighing 2714 g on 38w2d and insulin treatment was discontinued. A 75 g OGTT after delivery showed a normal glucose tolerance curve. This case suggests that some GDM subjects require more insulin during tocolysis than previously reported, and emphasizes the need to carefully observe such subjects during ritodrine hydrochloride and magnesium sulfate therapy.

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Bacterial aneurysm rupture, although relatively rarely seen in the daily clinic experience, often becomes critical and has high mortality. We report a case of bacterial cerebral aneurysm rupture after meningitis onset in a subject hospitalized for hypoglycemia. A 78-year-old man with type 2 diabetes mellitus was hospitalized in an emergency for prolonged hypoglycemia due to reduced appetite. On hospital day 10, he developed a high fever and pyuria. Antibiotic therapy did not alleviate the fever, however. On hospital day 17, the man developed nuchal rigidity and an increased cerebrospinal fluid cell count of predominantly polynucleated cells. He was diagnosed with bacterial meningitis and the related treatment initiated. On the morning of hospital day 20, respiratory arrest suddenly occurred and head computed tomography (CT) showed the onset of acute subarachnoid hemorrhage. Emergency craniotomy was done immediately and a diagnosis of bacterial aneurysm rupture was made. A bacterial cerebral aneurysm is difficult to detect before manifestation of an adverse episode. Our case strongly suggests the importance of considering the possibility of bacterial cerebral aneurysm when dealing with meningitis in subjects with diabetes mellitus.

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[in Japanese]

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[in Japanese]

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