Autonomic nervous dysfunction and peripheral neuropathy are often found in both diabetics and alcoholics. In the present study, we have attempted to assess whether and how autonomic nervous function is impaired in diabetes complicated by alcoholism (DM·AL). To that effect, the coefficient of variation of R-R intervals (CV_RR) was evaluated in these patients (n=68) on the 30th day of abstinence. Decreased CV_RR (CVRR<2.0) was more frequently found in DM·AL (49%) than in non-alcholic diabetics (DM, n=50, 22%, p<0.01) or non-diabetic alcoholics (AL, n=22, 9%, p< 0.01). Diminished vibration sence was more frequently found in DM·AL (47%) than in either DM (24%, p<0.05) or AL (9 %, p<0.01). In patients whose diabetic history was shorter than 3 years, autonomic nervous dysfunction and peripheral neuropathy were more frequently observed in DM·AL than in DM (CVRR<2.0: 48 % vs 9%, p< 0.01. Diminished vibration sense: 43% vs 14%, p< 0.05), while the prevalence of diabetic retinopathy did not differ between these two groups. Central nervous system damage, e. g. brain atrophy or dementia, was also associated with low CVRR in alcoholic diabetics. These data suggest that preexisting autonomic nervous dysfunction and peripheral neuropathy due to alcoholism are exacerbated by the concomitant presence of diabetes.

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Recently, the important role of the Maillard reaction in the development of diabetic complications has been attracting attention. The Maillard reaction is a non-enzymatic reaction between aldehyde groups of reducing sugars and free side chains on amino acids, especially lysine residues of proteins. We investigated the possible inhibition of the Maillard reaction by 1-lysine, which is one of the essential amino acids and is usually taken in through foods.
L-lysine increased the total fluorescence intensity of the incubation mixture, but slightly decreased the furosine level generated on BSA. L-lysine inhibited the glucose-induced polymerization of lysozyme and acted on 3-deoxyglucosone (3DG), an active cross-linker of the Maillard reaction, to inhibit the 3DG-induced polymerization.
Exogenously applied 1-lysine was considered to compete with lysine residues of protein for glucose and trapped active carbonyl intermediates. Thus, these results suggest that 1-lysine inhibits the Maillard reaction.

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We investigated the reliability of patient-generated data from self-monitoring of blood glucose (SMBG) in 17 patients with insulin-treated diabetes mellitus by means of a memory-reflectance meter with a storage capacity for blood glucose measurements with corresponding time and date.
The patients were not aware of the memory capacity and were instructed to continue their practice of recording blood glucose diaries. In order to assess the reliability of patient-generated data as recorded in the blood glucose diaries, all omissions, additions and alterations of test values were determined. The precision index, which is the percent of values identified in blood glucose diaries, and the in memory-reflectance meter correspondance was 71.8±32.3%(Mean±SD). The omission index, which is the rate of underreporting of SMBG measurements from blood glucose diaries, was 24.8±24.2%. The addition index, which is the overreporting rate of phantom values from blood glucose diaries, was 19.3±27.8%. These indices showed that there were false self-reported SMBG data
After the use of a memory-equipped reflectance meter was brought the patient's attention, the precision index was 97.6±5.5%, the omission index was 2.6±3.7%, and the addition index was 2.3±6.6%. That is, the reliability of self-reported SMBG data was significantly improved, and HbA1c and serum fructosamine levels were significantly decreased.
In an analysis of precision and omission indices insulin-treated diabetic patients were found to have changed unacceptable values to acceptable values or omitted unacceptable values in hypo-or hyperglycemic results. However in the addition index not only acceptable values but also unacceptably hyperglycemic values were added to the blood glucose diaries in type A, type C and type D, as confirmed by the Yatabe-Guilford personality (Y-G) test of diabetic patients.
These observations indicate that while there were many false self-reported SMBG data which were unacceptably hypo-or hyperglycemic values, the patient's knowledge of the use of a memory-equipped reflectance meter would decrease the amount of false self-reported data.

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To elucidate the solubility of circulating plasma soluble fibrin monomer complexes (SFMC) in advanced diabetic microangiopathy, 60 diabetic patients with various degrees of diabetic microangiopathy were studied. Their HbA₁ levels were under 10 %. Overnight fasting plasma levels of fibrinogen (Fbg), fibronectin (Fn) and SFMC were determined. Moreover, the constituents of SFMC were analysed by SDS-polyacrylamide gel electrophoresis, and the ratios of Fn to fibrin (ogen) and Fn to the α-fraction were evaluated because the solubility of SFMC is elevated with an increase in incorporation of Fn into fibrin complexes. Plasma Fbg, Fn and SFMC concentrations were elevated in proportion to the progression of diabetic retinopathy, i.e. the stage of retinopathy and the degree of proteinuria. Simultaneously, an increase in the ratios of Fn to fibrin (ogen) and Fn to the α-fraction in SFMC were observed. In addition, a pattern of noncovalent binding of Fn to fibrin in SFMC was recognizable. The percentage of the α-fraction in fibrin (ogen) did not change with the progression of diabetic microangiopathy. However, that of the Fn fraction in SFMC was elevated.
From these results, it seems that there is an increase in the binding of Fn with the α-fraction in fibrin (ogen), and SFMC with a high solubility is formed in circulating plasma in the advanced stages of diabetic microangiopathy. Such a status is thought to be a compensatory stage of chronic low grade disseminated intravascular coagulation.

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Islet amyloid polypeptide (IAPP or amylin) is the major protein component of the islet amyloid deposits found in patients with non-insulin-dependent diabetes mellitus (NIDDM). This peptide appears to be a normal product of the insulin-producing beta cell, and recent studies suggest that it may be involved in the pathogenesis of NIDDM. In this study, plasma IAPP, insulin (IRI) and C-peptide (CPR) concentrations at fasting and during an oral glucose load were measured in NIDDM patients to assess the characteristics of the peripheral levels of IAPP in NIDDM. In normal subjects, the fasting plasma IAPP level was 24.9±2.0 pg/m/(mean±SEM) and was about 1/7 of the IRI level on a molar basis. The fasting IAPP level was high in obese patients with NIDDM and low in patients with insulin-dependent diabetes mellitus. In non-obese patients with NIDDM, fasting IAPP levels were the same as those of non-obese control subjects, but the molar ratio of plasma IAPP to IRI (or CPR) was decreased. In obese patients who showed hyper-responsiveness of IRI relative to CPR, hyperresponsiveness of IAPP relative to CPR was noted after oral glucose loading. This study suggests that basal hyposecretion of IAPP, relative to insulin, exists in NIDDM and that IAPP may act physiologically with insulin to modulate glucose metabolism.

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Seven patients were studied to evaluate the effect of trimebutine maleate on diabetic diarrhea. All patients had severe autonomic neuropathy. Improvement was assessed on the basis of subjective symptoms (diarrhea score) after oral administration of trimebutine maleate (300 mg/day). Within two days, severe diarrhea was markedly reduced. No side effects were observed in any of the patients. The results of this study suggest that trimebutine maleate may serve as a useful drug in improving the symptom of diabetic diarrhea.

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We have studied the effect of camostat mesilate on microalbuminuria in patients with non-insulin-dependent diabetes mellitus. A randamised design was used. Forty three normotensive diabetic patients free of overt proteinuria were divided into two groups. One group was given camostat mesilate 300 mg/day and the other was treated as a control group. The age of the patients, the duration of diabetes, the glycemic control and the initial urinary albuminn excretion rate were matched in each group. Urinary albumin concentration was measured by RIA and the albumin creatinine ratio (ACR) was calculated to observe the effect of camostat mesilate on out patient clinic for six months.
In the group treated with camostat mesilate, ACR (mg/gCr) significantly (p>0.05) decreased from 75±50 to 53±43 (3 mo.) and to 37±20 (6 mo.). In those subjects with a relatively high ACR (ACR>100 mg/gCr), the decrease was more prominent with an average decrease of 65% after six months treatment. The control group showed no definite change in ACR through the six month period of observation. In conclusion, even short term treatment with camostat mesilate can reduce ACR in patients with incipient diabetic nephropathy. It is suggested that camostat mesilate caused a change in the glomerular capillary permeability for macromolecules through its inhibitory effects on the kallikrein-kinin system, complement system, coagulation system and platelet function.

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