Insulinoma in a patient with non-insulin-dependent diabetes mellitus

Insulinoma in a patient with pre-existing diabetes is exceedingly rare. Only a small number of well-documented cases have been reported in the world during the last 40 years. We describe a case with non-insulin-dependent diabetes mellitus who after seven years of sulfonylurea treatment experienced recurrent episodes of hypoglycemia. Endogenous hyperinsulinism was found and radiographical examination and transhepatic venous sampling confirmed an insulin secreting pancreatic tumor. After surgical excision of the tumor, patient was relieved from hypoglycemic attacks but required to initiate insulin injection for the treatment of hyperglycemia.     

Caries in patients with non-insulin-dependent diabetes mellitus

OBJECTIVE: To describe intratrial differences in hind limb symmetry in healthy dogs at the trot, using noninvasive, computer-assisted, three-dimensional kinematic gait analysis. ANIMALS: 8 clinically normal large-breed adult dogs. PROCEDURE: Dynamic flexion and extension angles and angular velocities were calculated for the coxofemoral, femorotibial, and tarsal joints of dogs at the trot. Temporal and distance variables were computed. Essential Fourier coefficients were used to determine mean flexion and extension curves for all joints and to compare differences in movement between right and left hind limbs. Variances attributable to limb, dog, and trial were determined. RESULTS: Each joint had a characteristic pattern of flexion and extension movement that was used to compare intratrial symmetry of hind limb gait. Significant differences were not detected in temporal or distance variables between the right and left hind limbs. Significant differences were not noted in essential Fourier coefficients used to characterize coxofemoral, femorotibial, and tarsal joint angles and angular velocities, with the exception of the cosine-0 coefficient for coxofemoral angular velocity. Variation in joint angle and angular velocity measurements were attributable to individual dog and trial. Variation attributable to limb was negligible. CONCLUSIONS: Intratrial evaluation of right-left hind limb symmetry, using kinematic gait analysis, indicated objectively that hind limb movement is symmetrical at the trot in healthy large-breed dogs. CLINICAL RELEVANCE: Documentation of hind limb symmetry at the trot will help provide a basis for direct comparison of both hind limbs in future studies evaluating gait and treatment of dogs with musculoskeletal disease.     

Early endothelial alterations in non-insulin-dependent diabetes mellitus

Nude mice were given AlPcS2a (aluminum phthalocyanine disulfonate) and AlPcS4 (aluminum phthalocyanine tetrasulfonate) by intraperitoneal injections. After time intervals of 1-48 hours the mice were exposed to 150 mW cm-2 light at 670 nm and the phthalocyanine fluorescence was measured during light exposure. During the first few minutes of light exposure the phthalocyanine fluorescence of the skin of the mice increased by up to a factor of two, indicating lysosomal localization of the dye and permeabilization of the lysosomes. The process did not occur in the skin of dead mice, indicating that the process was dependent on oxygen.     

Reduced myocardial flow reserve in non-insulin-dependent diabetes mellitus

OBJECTIVES: We analyzed myocardial flow reserve (MFR) in patients with non-insulin-dependent (type II) diabetes mellitus (NIDDM) without symptoms and signs of ischemia. BACKGROUND: Diminished MFR in diabetes has been suggested. However, it remains controversial whether MFR is related to glycemic control, mode of therapy or gender in NIDDM. METHODS: Myocardial blood flow (MBF) was measured at baseline and during dipyridamole loading in 25 asymptomatic, normotensive, normocholesterolemic patients with NIDDM and 12 age-matched control subjects by means of positron emission tomography and nitrogen-13 ammonia, after which MFR was calculated. RESULTS: Baseline MBF in patients with NIDDM ([mean +/- SD] 74.0 +/- 24.0 ml/min per 100 g body weight) was comparable to that in control subjects (73.0 +/- 17.0 ml/min per 100 g). However, MBF during dipyridamole loading was significantly lower in patients with NIDDM (184 +/- 99.0 ml/min per 100 g, p < 0.01) than in control subjects (262 +/- 120 ml/min per 100 g), as was MFR (NIDDM: 2.77 +/- 0.85; control subjects: 3.8 +/- 1.0, p < 0.01). A significantly decreased MFR was seen in men (2.35 +/- 0.84) compared with women with NIDDM (3.18 +/- 0.79, p < 0.05); however, no significant differences were found in terms of age, hemoglobin a1c and baseline MBF. MFR was comparable between the diet (2.78 +/- 0.80) and medication therapy groups (2.76 +/- 0.77) and was inversely correlated with average hemoglobin A1c for 5 years (r = -0.55, p < 0.01) and fasting plasma glucose concentration (r = -0.57, p < 0.01) but not age or lipid fractions. CONCLUSIONS: Glycemic control and gender, rather than mode of therapy, is related to MFR in NIDDM.     

Frequency of diabetes in family members of probands with non-insulin-dependent diabetes mellitus

OBJECTIVES: To describe the prevalence of known diabetes in a multi-ethnic community in South Auckland, New Zealand, in relation to family history of diabetes and past history of diabetes in pregnancy. DESIGN: A cross-sectional, household survey comparing ascertainment with local general practice diabetes registers where they existed. SETTING: An inner-city community with a high proportion of Maori, Pacific Islands people and Europeans. SUBJECTS: A total of 55,518 residents (91% response). Comparison with diabetes registers showed 91% ascertainment of known diabetic residents. More detailed interviews with 176/214 (82%) Europeans, 286/336 (85%) Maori and 495/585 (85%) Pacific Islands people with known diabetes. Fifty subjects had insulin-dependent diabetes mellitus on clinical criteria and were excluded from analyses. MAIN OUTCOME MEASURES: Prevalence of diabetes. RESULTS: Those with non-insulin-dependent diabetes mellitus were more likely to have a diabetic mother than father (Europeans, 21.7% vs. 9.9%; Maori, 17.6 vs. 11.4%; Pacific Islands, 15.7 vs. 5.3%). Diabetic women had a similar likelihood of having a diabetic father as diabetic men but were 1.84 times as likely to have a diabetic mother (95% CI, 1.27-2.69). Diabetic women with past diabetes in pregnancy had 2.05 (95% CI, 1.01-4.15) times the chance of a diabetic offspring as women who had not had past diabetes in pregnancy, who in turn had 2.69 (95% CI, 1.17-6.18) times the likelihood of having a diabetic offspring as diabetic men. CONCLUSIONS: The mother is a more important conduit for inheritance of diabetes than the father in these three ethnic groups. A history of diabetes in pregnancy confers an extra risk to the offspring above this usual maternal excess.     

Breastfeeding and incidence of non-insulin-dependent diabetes mellitus in Pima Indians

BACKGROUND: Early exposure to cow's milk has been implicated in the occurrence of insulin-dependent diabetes mellitus but there is little information about infant-feeding practices and subsequent non-insulin-dependent diabetes mellitus (NIDDM). We examined the association between breastfeeding and NIDDM in a population with a high prevalence of this disorder, the Pima Indians. METHODS: Glucose-tolerance status was obtained from a 75 g oral glucose-tolerance test. A standard questionnaire given to mothers was used to classify infant-feeding practices for the first 2 months of life into three groups; exclusively breastfed, some breastfeeding, or exclusively bottlefed. The association between the three infant-feeding groups and NIDDM was analysed by multiple logistic regression. FINDINGS: Data were available for 720 Pima Indians aged between 10 and 39 years. 325 people who were exclusively bottlefed had significantly higher age-adjusted and sex-adjusted mean relative weights (146%) than 144 people who were exclusively breastfed (140%) or 251 people who had some breastfeeding (139%) (p = 0.019). People who were exclusively breastfed had significantly lower rates of NIDDM than those who were exclusively bottlefed in all age-groups (age 10-19, 0 of 56 vs 6 [3.6%] of 165; age 20-29, 5 [8.6%] of 58 vs 17 [14.7%] of 116]; age 30-39, 6 [20.0%] of 30 vs 13 [29.6%] of 44). The odds ratio for NIDDM in exclusively breastfed people, compared with those exclusively bottlefed, was 0.41 (95% CI 0.18-0.93) adjusted for age, sex, birthdate, parental diabetes, and birthweight. INTERPRETATION: Exclusive breastfeeding for the first 2 months of life is associated with a significantly lower rate of NIDDM in Pima indians. The increase in prevalence of diabetes in some populations may be due to the concomitant decrease in breastfeeding.     

The computer support of hypoglycemic therapy in non-insulin-dependent diabetes mellitus

Computer program designed by the authors and described in the article is realized as a reference system providing data on combinations of drugs used for diabetes mellitus. The system supplies information on hypoglycemic effects of representatives from each of three groups (insulins, sulfonamides, biguanides) administered both separately and in association with second drug selected by user. Interface of the system (drug menus and output windows) is friendly and demand no special training and operating skill. The program is written in C language and compiled as a single executable module for IBM-compatible personal computers.     

Microalbuminuria in non-insulin-dependent diabetes mellitus. Implications for renal survival

Microvascular and macrovascular disease cause considerable mortality and morbidity both among patients with non-insulin-dependent diabetes mellitus and those with insulin-dependent diabetes mellitus. Furthermore, non-insulin-dependent and insulin-dependent diabetes mellitus overlap in their pathogenesis as well as short- and long-term complications. In the diabetic patient, genetic susceptibility as well as other factors, ie, microalbuminuria, hypertension, high protein intake, blood glucose control, etc, ultimately culminate in a diffuse disease process, eg, diabetic vascular and/or renal disease. Early predictors of susceptibility for development of renal disease in diabetic subjects would help focus our treatment strategies. The role of microalbuminuria as a prognostic marker for the major complications of insulin-dependent diabetes mellitus has been previously reviewed. We reviewed the role of microalbuminuria as prognostic marker for progression of diabetic renal disease in subjects with non-insulin-dependent diabetes mellitus. We examined treatment strategies to lower microalbuminuria and its associated impact on disease progression.     

The antidyslipoproteinemic activity of ufibrate in patients with non-insulin-dependent diabetes mellitus

Ufibrate (150 mg daily) was found to have a beneficial effect on main parameters characterizing lipid metabolism, with no effect being exerted on carbohydrate metabolism, as evidenced by three months' follow-up of 24 patients aged 42 to 65 presenting with insulin-nondependent type II diabetes mellitus and hyperlipidemia. Ufibrate appeared to be a most efficacious long-term drug treatment option, particularly so in those patients presenting with initially high blood levels of a great many of lipid fractions.     

Endothelium-dependent relaxation in peripheral vasculature and kidney of non-insulin-dependent diabetes mellitus

Desmopressin (DDAVP), an AVP.V2-receptor agonist, evokes endothelium-dependent relaxation (EDR) due to nitric oxide (NO), EDR factor (EDRF) in the systemic vasculature, and glomerular afferent arterioles via AVP receptor(s). Glyceryl trinitrate (GTN) causes endothelium-independent (nonreceptor-mediated) vasodilation. We elucidated the possible involvement of EDRF in early non-insulin-dependent diabetes mellitus (NIDDM) and glomerular hyperfiltration (GHF) by DDAVP and GTN infusions. Patients with advanced DM nephropathy (DM.Np) (n = 7) were also examined. DDAVP and GTN decreased the mean blood pressure in DM with GHF (DM + GHF) and without GHF (DM-GHF) greater than that in normal subjects (N), without any difference in the heart rate changes in any group. Plasma levels of cGMP, a cellular messenger of NO, were significantly increased by DDAVP and GTN with a similar increment in each group. DDAVP caused a significant increase in urinary cGMP excretion in each group with a similar increment in each group. However, it caused a transient increase in creatinine clearance only in DM + GHF although GTN did not, and an exaggerated excretion of urinary albumin in early NIDDM, especially in DM+GHF, without a change in beta 2-microglobulin excretion. In contrast, in DM.Np GTN caused a decrease in blood pressure and an increase in plasma cGMP levels, but DDAVP did not. In conclusion, in peripheral vasculature and kidney, an enhanced sensitivity of vascular smooth muscle to NO is present in early NIDDM. The exaggerated dilation of glomerular afferent arterioles by preferentially produced NO in in situ, which causes a rise in PGC, might be partly responsible for the glomerular hyperfiltration and subsequently the increase in the glomerular protein permeation of DM+GHF. However, in peripheral blood vessels of DM.Np EDR is impaired. Thus, EDR seems to change with the development of NIDDM.     

Beta-cell dysfunction in first-degree relatives of patients with non-insulin-dependent diabetes mellitus

To analyse the relationship between age, glucose tolerance, beta-cell function, and insulin sensitivity in preclinical states of non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), we have done a cross-sectional, age-stratified analysis of 86 non-diabetic first-degree relatives of NIDDM patients and 49 controls with similar age, sex, and BMI. A 5 mg kg ideal body weight-1 min-1 for 60 min of continuous infusion of glucose with model assessment (CIGMA) of serum glucose and C-peptide values at the end of the infusion was used to determine glucose tolerance and beta-cell function. Insulin sensitivity was estimated by modelling basal serum glucose and insulin values. Relatives and controls were divided into tertiles on the basis of age. Relatives had higher basal (5.3 vs 5 mmol l-1, p = 0.02) and achieved serum glucose (9.1 vs 8.4 mmol l-1, p = 0.01), lower beta-cell function (128 vs 145%, p = 0.007), and lower insulin sensitivity (37 vs 43%, p = 0.002). Beta-cell function declined with age in relatives (from 139% in young subjects to 134% in intermediate subjects and to 111% in older subjects, p = 0.002) and this decline was associated with an increase in basal serum glucose (from 5.1 to 5.3 and to 5.7 mmol l-1, p = 0.000) and achieved glucose (from 8.3 to 9.1 and to 9.3 mmol l-1, p = 0.038), without significant changes in insulin sensitivity. These trends were observed even after the exclusion of subjects with mild glucose intolerance. We conclude that both beta-cell dysfunction and insulin resistance are present in first-degree relatives of NIDDM. The progression of beta-cell dysfunction and glucose intolerance with age suggests that beta-cell dysfunction is the key factor in the apparition and progression of the disease.     

Genetic dissection of "OLETF", a rat model for non-insulin-dependent diabetes mellitus

Granulation tissue formation was studied in viscose cellulose sponges with different cellulose contents and sizes after subcutaneous implantation in rats. Samples were removed and studied histologically and histomorphometrically 1-16 weeks after implantation. The implants with lower cellulose content and smaller size were invaded by more cells and filled with connective tissue more rapidly than those with the higher content and larger size. In larger sponge implants the beneficial effect of the lower cellulose content was more conspicuous.     

Oral antihyperglycaemics. Considerations in older patients with non-insulin-dependent diabetes mellitus

Various instrumentation techniques have been proposed and examined with conflicting results. They include hand and ultrasonic techniques and combinations of the two. In the present study we assessed the effectiveness of four preparation methods for cleaning small, curved root canals, using backscattered-imaging scanning electron microscopy (SEM). The methods were: (i) step-back without initial coronal flaring; (ii) step-back with coronal flaring; (iii) step-back with initial coronal flaring and finished by ultrasonic irrigation; and (iv) ultrasonics only. Eighty freshly extracted maxillary and mandibular molars were randomly placed into four treatment groups of 20 teeth each. After preparation, roots were sectioned longitudinally and examined wet by SEM. Each canal was qualitatively evaluated and the groups compared for removal of debris and smear layer, both overall and at each level (apical, middle and coronal). There were no statistically significant differences between the techniques, either overall or within any of the regions. When comparing regions (regardless of technique) the middle level was cleaner than the apical or coronal levels. In conclusion, efficacy differed little among the techniques; none of them completely removed smear layer and all left debris.     

A risk-benefit appraisal of acarbose in the management of non-insulin-dependent diabetes mellitus

Acarbose is an alpha-glucosidase inhibitor proposed for the treatment of diabetic patients. It acts by competitively inhibiting the alpha-glucosidases in the intestinal brush border. The principal action of these enzymes is to convert nonabsorbable dietary starch and sucrose into absorbable monosaccharides (e.g. glucose). Enzyme inhibitors delay this conversion, slowing the formation and consequently the absorption of monosaccharides, and thus reducing the concentration of postprandial blood glucose. Both starch and sucrose are influenced, whereas lactose and glucose are not. Many studies in experimental animals, healthy volunteers and patients with non-insulin-dependent diabetes mellitus (NIDDM) have shown that acarbose decreases postprandial blood glucose, with a lesser reduction of fasting blood glucose, plasma triglycerides and postprandial insulin levels. In long term studies in NIDDM patients, acarbose significantly reduced glycosylated haemoglobin levels. Acarbose is only minimally absorbed from the gut and no systemic adverse effects have been demonstrated after long term administration. The drug allows undigested carbohydrates to pass into the large bowel where they are fermented causing flatulence, bloating and diarrhoea. These symptoms, which occur in approximately 30 to 60% of patients, tend to decrease with time and seem to be dose-dependent. They are minimised by starting therapy with low doses (such as 50mg 3 times daily) which may be effective in many patients. An increase in serum hepatic transaminases observed in earlier studies in the US, where doses of acarbose up to 900mg daily were used, has been not reported with the lower doses of the drug actually recommended [150 to 300mg (up to 600mg) daily]. In conclusion, acarbose may be useful in patients with NIDDM when diet alone is no longer able to maintain satisfactory blood glucose control. Furthermore, it may be a valid alternative to sulphonylurea or biguanide therapy when these drugs are contraindicated and insulin administration may be delayed. Acarbose seems also to be a useful adjunct to hypoglycaemic oral agents but its precise role in this field has not been fully clarified.     

Prevalence and aspects of arteriopathies in non-insulin-dependent diabetes mellitus with severe hypertension

Severe hypertension may lead to macroangiopathy complications especially when a major vascular risk factor as diabetes exists. We have studied the prevalence of macroangiopathy in a group of 40 consecutive NIDDM patients with severe hypertension (> or = 3 hypotensive drugs) (grS) that we have compared to 80 consecutive NIDDM patients with controlled hypertension (1 or 2 hypotensive drugs) (grC). All patients have had metabolic, blood pressure (ABPM) and vascular (color duplex) investigations. The two groups were similar for age (years): 61.9 > or = 9 versus 65.2 +/- 9.5, diabetes duration (years): 10.7 +/- 7 versus 12.1 +/- 8 and hypertension duration: (years) 8.9 +/- 8 versus 11.7 +/- 7.3. The mean level of blood pressure was the same in all patients (mmHg): SBP = 138 +/- 14 versus 144 +/- 20; DBP = 80 +/- 9 versus 83 +/- 13; MBP = 100 +/- 10 versus 105 +/- 15. The frequency (%) of escape SBP (> 140): 50 versus 80, p < 0.01), and DBP (> 90): 29 versus 35, p < 0.05 was significantly higher in grS. Twenty (25%) patients in grC and 20 (50%) in grS had one or more macroangiopathy which was dispatched as follow: coronary heart disease n = 8 (7%) versus 13 (32.5%), p < 0.01; lower limb arteritis n = 12 (15%) versus n = 9 (22%), NS; carotid atheroma n = 5 (25) versus n = 6 (15%), NS. All significant renal artery stenosis (RAS) n = 8 (20%) were found in grS (p < 0.001). Only plasma triglyceride level (mmol/L) was statistically higher in grS 2.5 +/- 1.2 versus +/- 1 while BMI, plasma cholesterol, HbA1C, and creatininemia were NS. The sex-ratio (F/M) 1.28 versus 3, insulin requirement (%): 11 versus 42.5, retinopathy (%) 14 versus 45 and micromacroalbuminuria were statistically significant p < 0.01. Conclusion: macroangiopathy is frequent in severe hypertension (50%) versus controlled hypertension (25%) in NIDDM patients especially coronary heart disease (32.5%); the prevalence of RAS is high in grS (20%). The following criteria are frequently noticed in high risk patients: insulin requirement, micro or macroalbuminuria and high plasma triglyceride.     

The esters of carboxylic nutrients as insulinotropic tools in non-insulin-dependent diabetes mellitus

1. In non-insulin-dependent diabetes mellitus, the pancreatic B-cell displays a preferential impairment of its secretory response to D-glucose. 2. A number of agents could be used to restore secretory activity in the diseased B-cell. 3. In this respect, esters of carboxylic nutrients, such as succinic or glutamic acid, present the advantages of stimulating both proinsulin biosynthesis and insulin release, remaining efficient in models of B-cell glucotoxicity, augmenting the secretory response to hypoglycemic pharmacological agents, protecting the B-cell against cytotoxic aggressions, and exerting a long-term beneficial effect upon the secretory potential of the endocrine pancreas. 4. Potential limitations of this new therapeutical approach, such as the generation of methanol from the esters, their postulated inefficacy after enteral administration, or the occurrence of extrapancreatic metabolic effects may be circumvented. 5. The esters of carboxylic nutrients could even be used in other cells endangered by ATP depletion.