Effect of multiple daily insulin injections on the course of diabetic retinopathy.

Forty-two diabetic patients on insulin once a day in the early stage of diabetic retinopathy were randomly assigned to one of two kinds of insulin regimen, i.e., single or multiple daily injections. Retinal changes were quantitatively estimated by counting the microaneurysms (MAs) observed on fluorescein angiograms at the posterior pole of the more diseased eye. Baseline characteristics of the two groups were not significantly different. These included duration of diabetes, age at diagnosis, daily dose of insulin, amount of urinary sugar excreted in 24 hours, fasting blood sugar (FBS), and number of MAs. During the follow-up (mean duration of three years) the mean yearly progression in the number of MAs was significantly less in the multiple- than in the single-injection groups: 1.8 +/- 0.7 versus 7.2 +/- 1.9 (p less than 0.01; nonparametric test: p less than 0.02). Final values were, respectively, MAs: 15.2 +/- 4.9; 33.0 +/- 7.9; glycosuria (gm./24 hrs): 20.6 +/- 2.5; 27.5 +/- 4.3; FBS (mg./100 ml.): 154 +/- 15; 195 +/- 11. P values comparing the two groups were less than 0.02, less than 0.02, and less than 0.05. Thus, in this clinical trial, made under routine treatment conditions, the use of divided daily insulin injections was effective in improving diabetic control and delaying retinal changes.

Correlation between the nature and amount of carbohydrate in meal intake and insulin delivery by the artificial pancreas in 24 insulin-dependent diabetics.

We have studied the effects of mixed meals and dextrose intake on blood glucose and insulin delivery by the artificial pancreas in 24 insulin-dependent diabetics. A group of 12 patients had 3 mixed meals containing at random 20, 40, and 60 g of complex carbohydrate along with protein and fat; another group of 12 diabetics, comparable in weight, age, and duration of diabetes, received at random 20, 40, and 60 g of dextrose. Dextrose ingestion led to a higher initial blood glucose increase than did the mixed meal, but the duration of blood glucose increase lasted significantly longer after the mixed meal than after the dextrose load. The areas under the curves of hyperglycemia were not significantly different. There was a high (but not linear) correlation between the total amount of insulin delivered in order to restore initial blood glucose values and the amount of CHO consumed. There was no correlation with age, body weight, duration of diabetes, nor with the nature and order of administration of the CHO load; 5.1 +/- 1.6 to 13.7 +/- 2.1 units of insulin were needed for a period of 94 +/- 11 to 132 +/- 11 min. It is suggested that some of the data obtained in this study might be useful in the programming of an open-loop insulin infusion system.

The search for an optimized treatment of hypoglycemia. Carbohydrates in tablets, solutin, or gel for the correction of insulin reactions.

Recommendations for the treatment of insulin reactions are based more on habit than data. We investigated the efficacy in correcting blood glucose levels and alleviating clinical symptoms of hypoglycemia of seven orally administered carbohydrates--glucose in solution, tablets, and gel; sucrose in solution and tablets; a hydrolized polysaccharide solution; and orange juice--each of which provided 15 g of carbohydrate. Forty-one type I diabetic patients recently treated with insulin agreed to submit to artificially induced hypoglycemia by an intravenous injection of insulin. Corrective therapy was given when patients experienced symptoms and asked for treatment. Mean blood glucose levels 10 minutes after ingestion were found to be similar whether correction was dispensed with the tablets and the solutions of glucose, those of sucrose, or the polysaccharide preparation. However, almost no increment was obtained at this time point with the gel or the fruit juice. Fifteen and 20 minutes after carbohydrate intake, blood glucose levels were higher with the tablet forms than with the solutions, although differences only became signifiant for sucrose. Glycemic responses were again consistently lower with the sucrose gel and the orange juice. Clinical symptoms were alleviated in 14.0 +/- 0.8 minutes (mean +/- SEM) with sucrose and glucose in solution or tablets. We conclude that in moderately severe hypoglycemia, ingestion of 15 g of carbohydrate in the form of glucose or sucrose tablets or as a solution provides an effective therapy; both sugars seem equivalent. Even if sucrose lumps are better recommended in terms of cost and availability, they may not be recommendable in terms of palatability. Glucose gel or orange juice cannot be recommended, at least in light of our experimental procedure and at the dosage used therein.

Plasma insulin and C-peptide levels during continuous subcutaneous insulin infusion.

A study was performed to estimate the absorption kinetics of insulin infused subcutaneously. Four insulin-dependent diabetic subjects had their insulin pumped through a subcutaneously implanted fine polyethylene catheter at a constant rate of 5.0 +/- 0.3 ml/h but at two different insulin concentrations: 218 mU/ml between meals, and 2400 mU/ml at the start of breakfast, lunch, and dinner (lasting 20, 30, and 30 min, respectively). The amount (40 U/day) and distribution of insulin delivered was identical in the four patients in order to facilitate comparison between the subjects. No attempt was made to normalize their blood glucose during the study period. A study of the kinetics of insulin absorption was made by assaying plasma insulin levels; lack of plasma anti-insulin antibodies was verified; plasma C-peptide levels were measured and were far below values observed in the fed state in nondiabetic patients. The mean maximum insulin level reached after switching from low to high concentration insulin was observed 87 +/- 2 min after breakfast, 117 +/- 22 min after lunch, and 125 +/- 20 min after dinner. Differences observed are not significant. These values are similar to those observed after subcutaneous injection of 40 U/ml Regular insulin as a single bolus. After switching from high to low concentration, plasma insulin levels did not return to their basal values before the third or fourth hour. Subcutaneous insulin infusion could be a safe and easy way of insulin administration in an open-loop system; however, this method does not seem to be suitable for a closed-loop system.

Quantification of early subclinical limited joint mobility in diabetes mellitus.

Limited joint mobility (LJM) has been described in juvenile diabetic patients by Rosenbloom et al.; similar abnormalities are also present in adult diabetes. This modification may be associated with a high risk of microvascular complications. We tested the use of a goniometer in measuring subclinical joint limitation in 50 adult diabetic patients without overt, i.e., clinically evident, LJM as described by these authors. This diabetic population was compared with 118 nondiabetic adult controls. We found significant changes in hand mobility between the two groups for wrist flexion and extension of the 3rd and 5th fingers (P less than 0.001). Age was correlated to wrist flexion, wrist extension, and proximal interphalangeal flexion of the little finger. Wrist extension correlated with duration of diabetes (r = -0.37, P less than 0.01). Heavy manual activities significantly limited all motions except wrist and 5th finger metacarpophalangeal flexion. Early systematic examination by goniometry may prove to be a sensitive, quantitative, and inexpensive way of detecting joint stiffness at an early stage.

Lack of detectable deleterious effects on metabolic control of daily fructose ingestion for 2 mo in NIDDM patients.

The effects of a daily intake of 30 g fructose on blood glucose regulation, erythrocyte insulin receptors, and lipid metabolism have been studied in type II (non-insulin-dependent) diabetic subjects. Eight well-controlled patients received, in a randomly assigned crossover design over two 2-mo study periods, 30 g of fructose in exchange for an isocaloric amount of starch. Fructose could be taken at any time during the day as part of the 1400-1600 kcal allowed diet (50% carbohydrate, 30% fat, 20% protein). No significant difference was observed concerning body weight, HbA1c, fasting plasma glucose, fasting plasma insulin, uric acid, total cholesterol, high-density lipoprotein cholesterol, and triglycerides, nor was there any change in insulin binding to erythrocytes between the fructose and the control starch period. However, the mean plasma triglyceride levels after the fructose period, although still in the normal range, were significantly higher than baseline values (P less than .05). We conclude that moderate amounts of fructose incorporated into the diet of well-controlled type II diabetic subjects have no significant deleterious effect on glycemic control, insulin receptors of erythrocytes, or lipid metabolism.

Relative sweetness of fructose compared with sucrose in healthy and diabetic subjects.

Fructose is credited with some advantages over sucrose: it causes less of an increment in plasma glucose and insulin response, and the taste is sweeter. We reevaluated the latter property with a new methodology (the "up and down" method adapted from Dixon) in 33 healthy subjects, 17 insulin-dependent diabetes mellitus (IDDM) patients, and 12 non-insulin-dependent diabetes mellitus (NIDDM) patients. Sweetening potency was determined over 2-3 test sessions in each subject. Results are expressed in percent as the relative sweetness (R) of fructose (F) over sucrose (S), taken as reference. In the first set of experiments, with a 30-g/L sucrose-water solution at pH 7, we found that R values were similar for healthy subjects (102 +/- 8%) and diabetic subjects (106 +/- 7%) (P less than .05). No significant difference between IDDM and NIDDM patients was observed. In a second set of experiments, performed in healthy subjects only, R was increased in acid water (114%; P less than .01), in lemon juice (136%; P less than .001), in water at 2 degrees C (130%; P less than .001), and in coffee at 2 degrees C (120%; P less than .02); mean values were decreased in grapefruit juice (77%; P less than .001), in water at 43 degrees C (88%; P less than .01), and in coffee at 53 degrees C (87%; P less than .001). We found that the test methodology had a very satisfactory intrasubject reproducibility (coefficient of variation [C.V.] less than 8%) but a very wide intersubject variability (C.V. congruent to 32%).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulinemic and glycemic indexes of six starch-rich foods taken alone and in a mixed meal by type 2 diabetics.

The glycemic index concept neglects the insulin secretion factor and has not been systematically studied during mixed meals. Six starch-rich foods were tested alone and in an isoglucido-lipido-protidic meal in 18 NIDDs and compared with a glucose challenge. These test meals were randomly assigned using a three factor experiment design. All three tests contained 50 g carbohydrate; mixed meals were adjusted to bring the same amount of fat (20 g), protein (24 g), water (300 mL), and calories (475 kcal) but not the same amount of fiber. Whatever the tested meals, foods elicited a growing glycemic index hierarchy from beans to lentils, rice, spaghetti, potato, and bread (mean range: 0.21 +/- 0.12-92 +/- 0.12, p less than 0.001). Mixing the meals significantly increased the insulinemic indexes (p less than 0.05) and introduced a positive correlation between glycemic and insulinemic indexes (n = 6, r = 0.903; p less than 0.05). The glycemic index concept remains discriminating, even in the context of an iso-glucido-lipido-protidic meal. Insulinemic indexes do not improve discrimination between foods taken alone in type 2 diabetics: they only discriminate between foods during mixed meals, similarly to glycemic indexes.

Handedness, immune disorders and information bias.

In order to investigate the relations between handedness and migraine or immune disorders, we performed a case control study comparing the handedness of patients suffering from systemic lupus erythematosus (SLE), type I diabetes, Graves' disease, or migraine to that of a random sample of controls from the general population. A handedness index was measured from a 10-item questionnaire. No significant difference was observed. But when the controls who denied having ever suffered from migraine or any allergic disease were set apart from those who gave at least one positive answer to the same questions, the former were found more right-handed, i.e. with a lower handedness index than the latter (P less than 0.05) and than the SLE patients (P less than 0.05). More generally, the mean observed handedness index of controls giving a positive answer to any question about their health was found repeatedly higher than that of controls giving a negative answer: this was observed for 27 of the 32 questions. These results are highly suggestive of an information bias, the subjects saying they use the right hand for each of the 10 activities considered in the questionnaire being more likely to deny having suffered from a given disease or used, more or less recently, some drug or medical service. Our conviction is that previous observations dealing with the same topic are also more easily explained by the presence of an information bias than by Geschwind's theory. The implications for the design of further epidemiologic studies are discussed.

[Effects of deprivation and replacement by percutaneous 17 beta estradiol and oral progesterone on blood pressure and metabolic parameters in menopause patients with non-insulin-dependent diabetes]. / Effets de la substitution par 17 beta estradiol percutané et progestérone orale sur la pression artérielle et les paramètres métaboliques chez des patientes ménopausées diabétiques non insulinodépendantes.

The main purpose of this randomized controlled study was to assess the effects of postmenopausal estrogen replacement therapy on blood pressure (BP) and plasma renin substrate (PRS) in non insulin-dependent diabetic patients (DNID). We randomized 32 postmenopausal DNID (mean age: 55.3 +/- 4.2 years) into two groups: 16 women were untreated, and 16 received percutaneous estradiol (E2) 17 beta and natural progesterone for 6 months. Systolic (SBP) and diastolic (DBP) blood pressure were monitored by an automatic device at inclusion and on the 1st, 3rd and 6th months of therapy. Treatment efficacy was proven by significant E2 plasma increase to 92.2 +/- 13.4 pg/ml in the treated group, which is a sufficient level for preventing postmenopausal osteoporosis. No significant inter or or intra-individual variation in SBP or DBP was observed in either group. The same stability was noted for plasma renin substrate. No significant difference was noted between the two groups in terms of body weight, fructosamine and glycosylated hemoglobin A1c after 1, 3 and 6 months. There was also no change in plasma levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and apolipoproteins A1 and B. All the patients who received replacement therapy wished to continue treatment. We conclude that the association of percutaneous E2 17 beta and natural progesterone had no deleterious effects, in diabetic patients, on BP, carbohydrate and lipoprotein metabolism. Thus this postmenopausal replacement therapy appears preferable in this vascular high risk population, particularly since estrogens via the parenteral route may have an antiatherogenic effect by direct action on the vessel walls.

[Results of oral glucose tolerance tests in 123 cases of senile cataract with associated glucose metabolism disorders]. / Cataracte sénile et troubles du métabolisme glucidique étudiés par l'épreuve d'hyperglycémie provoquée par voie orale; à propos de 123 cas.

Systematic oral glucose tolerance tests in patients due for operation for senile cataract revealed the presence of latent diabetes, undiagnosed by standard investigations, in 20% of cases. The proportion of diabetics in patients with cataract is abnormally high when compared to a population free from cataract (43% as against 16%), which is in favor of a diabetic condition being the cause of lens opacification. An H.G.P.O. is therefore justified in all patients over 50 years of age with cataracts, especially those that are bilateral and mainly cortical.

[Effect of clinical hyperthyroidism and hypothyroidism on patent diabetes. 59 cases]. / Retentissement de l'hyperthyroïdie et de l'hypothyroïdie cliniques sur le diabète patient. Cinquante-neuf observations.

Fifty-nine patients with both clinical evidence of thyroid dysfunction and patent diabetes mellitus were investigated in our diabetology department. Patients with euthyroid goitre and iatrogenic or pituitary hypothyroidism were excluded from the study. Among the 45 diabetics with hyperthyroidism, 32 had Graves' disease and 13 had toxic adenoma; 71% were insulin-treated. Hyperthyroidism had passed unnoticed in 7 of these 32 patients because fatigue and loss of weight, which initially were the predominant or sole symptoms, are extremely frequent in uncontrolled diabetes. These symptoms, as well as polyuria, polyphagia and even sweating are common to both diseases. Considerable deterioration in the control of glycaemia was observed in 63% of the insulin-treated patients when hyperthyroidism developed, with a 17 to 212% (mean 82%) increase in insulin dosage in 53%. There was no correlation between the degree of hyperthyroidism and the loss of control. Following treatment of the hyperthyroidism, control was improved in 63%, with an 11-83% (mean 44%) decrease in insulin dosage in 59% of them. Insulin therapy could be withdrawn in only one of the 32 insulin-treated patients. Non-iatrogenic primary hypothyroidism was found in 0.2% of the diabetics investigated. This incidence was significantly higher than the calculated probability of the two diseases occurring by chance in the same patient. Eleven out of 14 patients were insulin-treated. When hypothyroidism developed, 73% of them had their insulin dosage reduced, with a high frequency of hypoglycaemic disorders: repeated "malaise" in 55% and coma in 27%. A higher proportion of vitiligo was also noted: 14% in the total patient population reported, and 18% in insulin-treated patients.

[Conception and contraception in diabetics]. / Conception et contraception chez les diabétiques.

PIP: Pregnancy in the diabetic women must be well-planned since it is crucial that the conception coincide with a period of perfect glycemic equilibrium. Contraception should be suspended only when the decision to conceive is made and the metabolic control is obtained. Currently, the mechanical and hormonal means of contraception (low-dose progestogen only) are the ones most commonly used. The child of a diabetic mother is open to risk for malformations, the result of hyperglycemia in the early stages of embryonic development. Impotence can plague the diabetic male's sex life. This is seen especially in autonomic diabetic neuropathy, in particular when there are severe urinary disorders. However, nonspecific causes for impotence are frequent in the diabetic male population and should be systematically investigated. (author's modified)^ieng