The role of diabetes mellitus in atherosclerotic disease found in familial hypercholesterolemia (FH) was investigated by comparison between FH with and without diabetes mellitus. The subjects consisted of 15 FH patients with diabetes mellitus (5 males and 10 females), 20 FH patients with impaired glucose tolerance (IGT)(16 males and 4 females) and 51 FH patients without diabetes mellitus (24 males and 27 females).
There were no significant differences in serum lipids, lipoprotein-lipids or apolipoprotein concentrations between groups with and without diabetes mellitus. The Achilles tendon was thicker and the incidence of cerebrovascular accidents was higher in the group with diabetes mellitus.
Sex-, age-, body mass index-, and total cholesterol-matched comparison was made between the 15 FH patients without diabetes mellitus and the 15 FH patients with diabetes mellitus. There were no significant differences between LDL-cholesterol, HDL-cholesterol or triglyceride and the incidence of hypertension. The Achilles tendon was thicker, pulse wave velocity was more accelerated, and the incidence of cerebrovascular accidents was significantly higher in FH with diabetes mellitus.
Because of the thickening of the Achilles tendon in spite of the same level of plasma lipids, some factor other than plasma lipids (possibly the arterial wall) in diabetes mellitus must be considered responsible for lipid deposition.

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Urinary glycylprolyl dipeptidylaminopeptidase (U-GP-DAP) activity has been shown to be an indicator of renal damage. In order to evaluate the clinical significance of U-GP-DAP in diabetic nephropathy, U-GP-DAP activity was compared with AER in timed overnight urine samples from 155 diabetics and 21 healthy controls. The diabetic patients were classified into the following three groups: normoalbuminuric (AER<=20μg/min), microalbuminuric (20μg/min<AER 200μg/min), and macroalbuminuric (AER 200 μg/min) groups. The U-GP-DAP activity in patients with normo-, micro-and macroalbuminuria were 16.11±6.50, 30.98±16.82, and 69.86±27.48 U/g. cre (mean+SD) respectively. These were significantly higher than those levels in normal controls (12.30±4.28 U/g. cre), and activity increased in parallel with the AER (r=0.697, p<0.001). There were exceptional cases: 17% of the 119 diabetics with normoalbuminuria showed high U-GP-DAP activity, and 10% of the 110 diabetics with normal U-GP-DAP activity (U-GP-DAP<=20.86 U/g. cre, mean+2SD) had a high AER. It is necessary for these cases to be examined further in the future. The changes in U-GP-DAP activity did not reflect acute changes in blood glucose and blood pressure. In conclusion, the significant positive parallelism of U-GP-DAP activity with AER in the diabetic may indicate that U-GP-DAP activity can be a useful indicator of early diabetic nephropathy.

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The hypothesis that adrenalectomy (ADX) improves insulin resistance in obesity was tested. Female ddY obese mice were used which had received administration of gold thioglucose (800 mg/kg) 6 weeks previously. Adrenalectomy and sham operations (Sham) were performed 2 weeks prior to the experiment. We studied glucose uptake and 2-deoxyglucose (2DG) uptake in basal and insulin-stimulated states (1mU/m/) using perfused hindquarter preparations. Two-deoxyglocose uptake was measured by measuring 2DG-6 phosphate (2DGP) accumulation after tritium-labeled 2DG infusion. The glucose uptake and 2DGP accumulation rate in the GTG-Sham group was significantly reduced not only in the insulin-stimulated state but also in the basal state. The glucose uptake and 2DGP accumulation in the GTG-ADX group were improved to the levels of the control (C-Sham) group in both basal and insulin-stimulated states. Both blood insulin and corticosterone levels of GTG obese mice were higher than those of control mice. Adrenalectomy diminished hypercorticism and reduced hyper-insulinemia in GTG obese mice.
These results suggest that hypercorticism contributes to insulin resistance in the skeletal muscles of gold thioglucose-induced obese mice.

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We measured spinal cord conduction velocity in 47 diabetic patients using somatosensory evoked potentials (SEP) following posterior tibial nerve stimulation. This investigation was performed in comparison with 30 normal subjects. Cortical SEPs were recorded at the foot sensory area (FS) and spinal SEPs were recorded at the 7th cervical vertebra (C₇) and at the 12th thoracic vertebra (Th₁₂). All peak latencies at FS, C, and Th₁₂ were considerably delayed in diabetic patients. The period of delay in peak latency was related to the duration of diabetes (p<0.01). Spinal cord conduction velocity (SCCV) was calculated from peak latency between Th₁₂ and C₇. The SCCV was 39.9±6.6 m/sec in diabetic patients and 44.5± 5.6 m/sec in normal subjects. The SCCV of diabetic patients was considerably slower than that of normal subjects (p<0.05). The delay in SCCV in diabetic pationts had a significant correlation with the duration of diabetes and fasting blood glucose concentration. The SCCV, however, did not have a significant correlation with sural nerve coduction velocity or the coefficient of variation R-R.
We concluded that diabetic myelopathy may be independent of peripheral neuropathy and autonomic nerve damage.

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Glucose intolerance associated with liver cirrhosis (LC) may be a primary metaboolic disorder or secondary due to LC. We compared clinical data on first admission in 8 patients with LC which became complicated by an overt diabetic state in the follow-up period (PDM group) with that in 22 patients with LC never complicated by a diabetic state (NDM group), using multivariate analysis. Seven variables (history of alcohol intake, age, basal blood glucose (BG) and IRI levels, EBG, EIRI and delayed peak BG time at and after 90 min in 75 g OGTT) discriminated the PDM and NDM groups significantly (correct interpretation rate 83.3% on internal checking) in discriminant analysis. Quantification analysis (Hayashi II) revealed that important variables defining the PDM group were a history of alcohol intake, basal IRI≥15μU/ml, age≥60 years, ΣBG≥1000mg/dl and peak IRI time at and after 120 minutes. Our results indicate that the glucose intolerance associated with liver cirrhosis could be judged as primary or secondary using clinical data and various variables on 75 g OGTT.

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Phenotypic changes in arterial smooth muscle cells (SMC) in diabetic animals were studied with regards to cell proliferation in order to clarify the mechanism of diabetic macroangiopathy. Diabetes was induced in rats by an intravenous injection of streptozotocin. SMC were cultured from the aorta using an explant method. Cell proliferation was measured by either outgrowth rate in the primary culture or cell replication in the subculture.
The SMC in diabetic animals outgrew faster from explant and also grew faster in subculture up to the 4th passage, than did those from non-diabetic animals. The enhanced growth property was observed 3-12 weeks after streptozotocin injection. Preincubation of SMC with serum from diabetic animals did not result in enhancement of growth properties. However preincubation with a high glucose medium did cause enhancement. Insulin therapy administered to the diabetic animals inhibited the enhancement of growth properties of SMC.
The above results suggested that diabetic SMC acquired accelerated growth properties, and these play an important role in the formation of diabetic macroangiopathy. The mechanism of such phenotypic changes in SMC is unknown but may be due in part to high blood glucose levels in diabetes mellitus.

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We have calculated a mean or delta mean daily fasting blood glucose level ([G] or Δ[G]) using assayed HbA1c levels and kinetic constants of hemoglobin A₁c (HbA₁c) synthesis.[G] levels ([G]-Lcal. or [G]-Scal.) were calculated at an optional time point (t) from labile or stable HbA1c values [H=G]e[H]or[HG]/[H], respectively, by
[G]-Lcal.=K_-1[H=G]e/[H]/K₁, or[G]-Scal=K_-1[HG]/[H]/_K1K2t
Δ[G]levels(Δ[G]-Lcal.or Δ[G]-Scal.)were calculated after a certain period of Δt from/Δ[H=G]e/[H]orΔ[HG]/[H], respectively, by
Δ[G]-Lcal.=K_-1Δ[H=G]E/[H]/K₁, or Δ[G]-Scal.=K_-1Δ[HG]/[H]/K_1K2Δt
Correlations between assayed and calculated [G] values by these formulas in NIDDM patients at t were as follows; y=0.97x+19.0 (r=0.789, n=60), y=0.62x+95.5 (r=0.626, n=60), respectively. Those in patients with improved or aggravated diabetic control after Δt were as follows; y=1.04x+2.9 (r=0.745, n=35), y=1.11x+24.1 (r=0.691, n=26), or y=1.02x+19.4 (r=0.558, n=18), y=1.22x+3.9 (r=0.753, n=14), respectively. Correlations were statistically significant.
We conclude that the calculation of a mean or delta mean daily fasting blood glucose level from labile or stable HbA1c and their changes by the proposed formulas are useful to attain diabetic control.

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Although patients with myotonic dystrophy (MD) are known to frequently have insulin resistance and glucose intolerance, cases of MD complicated by established diabetes mellitus seem to be rare.
A 36 year-old-female with primary amenorrhea and a known history of 12 years of NIDDM had been complaining of muscle weakness and visual disorders for 5 years. On admission she exhibited muscle weakness, muscle wasting, percussion myotonia and grip myotonia. EMG examination showed myotonic discharges and muscle biopsy revealed myotonic discharges and muscle biopsy revealed pathohistological findings characteristic of MD. Her diabetes had been poorly controlled with a plasma glucose of 430 mg/dl an HbAic 12.5% on admission. Ophthalmoscopic examination revealed findings characteristic of background diabetic retinopathy (Scott II a) and cataracts. She also had diabetic proteinuria and peripheral neuropathy. Endocrinological examination revealed hyperprolactinemia and hypergonadotropic hypogonadism. Urinary C-peptide excretion was 5-16, μg/day. A euglycemic glucose clamp study showed marked insulin resistance, whereas erythrocyte ¹²⁵I-insulin binding was normal. It appeared that diabetic metabolism in this case may be modified by MD, hyperprolactinemia and hypergonadotropic hypogonadism. This is the first case report of MD comlicated by established non-insulin-dependent diabetes mellitus with diabetic retinopathy.

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A 28-year-old male with insulin-dependent diabetes mellituns was admitted for live donor renal transplantation. His cardiac function was already impaired before commencing hemodialysis, and it markedly deteriorated with left ventricular dilatation and a reduced ejection fraction of 21% during the course of hemodialysis. The decreased cardiac function was attributed to noncompliance with the strict diet therapy of dialysis. By intensive water restriction and hemodialysis for the three months after admission, the cardiac function was improved with an ejection fraction of 45% and renal transplantation was performed. After renal tranplantation, overhydration and hypertension disappeared, resulting in the normalization of left ventricular size and decreased cardiac contractility. Thus, renal transplantation resulted in cardiac improvement in a diabetic with severely impaired cardiac function.

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To investigate the mode of inheritance of pancreatic lesions in male WBN/Kob rats, WBN/Kob rats were crossed with DA rats. Pancreata from male rats of backcross generation between Fl and WBN/Kob rats were examined histologically at 12 months of age. In 46 out of 92 (50.0 %) backcross generations, inflammatory cell infiltration and/or pancreatic fibrosis with deposition of hemosiderin, characteristic histological features of WBN/Kob strain, were observed. Namely, the presence/absence ratio of pancreatic lesions was nearly 1: 1 in the backcross generation. However, in another 4 out of 12 (33.3 %) in the Fl generation, pancreatic lesions were observed.
From the data of back crossing we may conclude that one recessive gene is responsible for expression of pancreatic fibrosis in male WBN/Kob rats. As for the occurrenece of pancreatic lesions in the Fl generation some modification of recessive type of inheritance is necessary. Further investigation is necessary to clarify this phenomenon.

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