Mean Plasma Glucose Levels Research Articles

Is sulphonylurea therapy effective long term? A 3-year study with gliclazide.

Fifty non-insulin-dependent diabetic patients, aged 59.06 +/- 1.37 years and overweight (119.3% of ideal body weight), with an impaired daily glycaemic profile despite a carbohydrate restrictive diet were treated with gliclazide (40 to 320 mg per day) for 36 months. Forty-four patients completed the full study (3 drop-outs for secondary failure, 3 others for reasons not related to the treatment). Mean daily plasma glucose levels (fasting, 10.00, 12.00 and 16.00 hours) decreased significantly from 15.2 +/- 0.7 to 6.9 +/- 0.2 mmol/l after 36 months. Mean fasting plasma glucose level decreased significantly from 12.7 +/- 0.5 to 8.2 +/- 0.2 mmol/l after 3 months and continued to decrease to 6.9 +/- 0.3 mmol/l after 36 months (p less than 0.01). Fatty acids, cholesterol, and triglycerides plasma levels also decreased significantly from 0.53 +/- 0.06 mmol/l, 6.3 +/- 0.2 mmol/l and 1.9 +/- 0.2 mmol/l, respectively to 0.32 +/- 0.01 mmol/l, 5.8 +/- 0.1 mmol/l and 1.6 +/- 0.1 mmol/l, respectively. No weight gain was observed: mean body weight decreased significantly from 68.2 +/- 1.7 to 64.0 +/- 1.4 kg, indicating that gliclazide did not interfere with diet-induced weight loss. Importantly, platelet adhesiveness, abnormal before treatment 77.2 +/- 1.3% (normal less than 70%), improved throughout the study to 57.8 +/- 1.3% after 36 months of gliclazide. Treatment was well tolerated and no hypoglycaemic attacks or other side-effects were reported.

Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus.

To assess the effects of very low caloric (VLC) diets on glucose homeostasis in noninsulin-dependent diabetes mellitus, 30 obese subjects with NIDDM were studied for 40 days while eating a 330 Cal/day diet, with a subgroup of 12 subjects further evaluated during 40 days of refeeding. All subjects successfully lost weight, with an average weight loss of 4.6 +/- 0.2 kg (+/- SEM) after 10 days, 7.1 +/- 0.3 kg after 20 days, and 10.5 +/- 0.4 kg after 40 days of VLC diet therapy. Thus, weight loss was steady and progressive throughout the diet period. In contrast, the majority (87%) of the reduction in mean fasting plasma glucose (FPG) levels (297 +/- 13 to 158 +/- 10 mg/dl; P less than 0.001) occurred after 10 days of VLC diet therapy, with a further reduction in glucose levels to 138 +/- 9 mg/dl on day 40. The FPG response measured after 10 days of VLC diet was unrelated to the degree of obesity, rate or extent of weight loss, or prevailing insulin levels, but did correlate significantly with the initial FPG level (r = 0.37; P less than 0.05) and duration of diabetes (r = 0.42; P less than 0.05). After discontinuation of the VLC diet and refeeding of an isocaloric (weight maintenance) diet in 12 subjects, a variable increase in the FPG occurred, with an average increase of 80% after 40 days of refeeding. However, the mean FPG level after 40 days of refeeding was still markedly lower than that before VLC diet therapy (254 +/- 20 vs. 167 +/- 14 mg/dl; P less than 0.02) despite withdrawal of antidiabetic medication in all subjects. The basal hepatic glucose output (HGO) fell rapidly from 149 +/- 13 to 81 +/- 5 mg/M2 X min (P less than 0.001) after 10 days of VLC diet and rose from 67 +/- 4 to 88 +/- 7 mg/M2 X min (P less than 0.001) after 10 days of refeeding. Basal HGO demonstrated a highly significant positive correlation with FPG levels (r = 0.89; P less than 0.001) before and during both VLC diet therapy and refeeding. A significant correlation was also found between the change in FPG level and the change in basal HGO (r = 0.84; P less than 0.001) during both VLC diet and refeeding. Compared to that before the VLC diet, glucose tolerance to mixed meals was markedly improved during the refeeding period, with no change in circulating insulin levels.(ABSTRACT TRUNCATED AT 400 WORDS)

U.K. Prospective Diabetes Study: II. Reduction in HbA1c with Basal Insulin Supplement, Sulfonylurea, or Biguanide Therapy in Maturity-onset Diabetes

Newly presenting maturity-onset diabetic subjects were put on diet and if, after 3–4 mo, their fasting plasma glucose continued >6 mmol/L, they were randomized to three therapies: (1) continuing diet alone, (2) with additional sulfonylurea, or (3) with additional basal insulin supplement provided by ultralente insulin. Obese patients were also randomized to metformin therapy. The aim was to lower the fasting plasma glucose to <6 mmol/L and the degree to which this reduced the hemoglobin A1c (HbA1c) concentration was studied in 195 patients over 1 yr. Sulfonylurea and insulin similarly reduced (P < 0.001) the fasting plasma glucose from 8.3 ± 1.9 to 6.7 ±1.3 mmol/L (mean ± 1 SD) and 8.6 ± 2.2 to 6.8 ±1.4 mmol/L, respectively. This was accompanied by a significant reduction (P < 0.001) of the HbA1c to the high normal range, from 9.1 ± 2.1% to 7.8 ± 1.2%, and from 9.1 ± 1.9% to 8.1 ± 1.3%, respectively, both values at 1 yr being significantly (P < 0.05) lower than in patients randomized to diet alone. Patients randomized to diet alone had little change in fasting plasma glucose (8.6 ± 1.8 to 9.3 ± 2.3 mmol/L) or HbA1c (8.8 ± 1.7% to 9.1 ± 1.6%, respectively). Thus, the simple therapeutic aim of trying to reduce the fasting plasma glucose to <6 mmol/L is an effective means of reducing the HbA1c to a high-normal level. The HbA1c and fasting plasma glucose concentrations were similarly related for all three therapies (HbA1c [%] = 0.47 × fasting plasma glucose [mmol/L] + 4.7). If the fasting plasma glucose concentration after dieting was >10 mmol/L, maximal-dose sulfonylurea therapy rarely reduced the fasting plasma glucose to 6 mmol/L and such patients could be started on maximum sulfonylurea therapy. Similar patients randomized to a basal insulin supplement alone required high insulin doses (mean 25 U/day), and also had mean fasting plasma glucose and HbA1c levels above the normal range.

Sucrose or honey at breakfast have no additional acute hyperglycaemic effect over an isoglucidic amount of bread in type 2 diabetic patients.

Exclusion of simple sugars from the diabetic diet is not always followed by patients and may not even be as crucial as was hitherto thought. We tested three types of mixed breakfasts (400 kcal, 50 g HCO) including an isoglucidic amount either of white bread (30 g), honey (20 g) or sucrose (15 g), at the critical morning period i.e. for breakfast, in a group of 21 Type 2 (non-insulin-dependent) diabetic patients (6 well- and 15 badly controlled). Mean plasma glucose and insulin levels were comparable on the three occasions: respectively with bread, sucrose and honey, peak glucose values were 18 mmol/l, 17.7 mmol/l and 17.5 mmol/l in the uncontrolled group versus 13.9 mmol/l, 12.8 mmol/l and 12.7 mmol/l in the well-controlled group. Peak insulin values were 33.6 mU/1,34.0 mU/l and 36.3 mU/l (p greater than 0.05) in uncontrolled patients against 57.5 mU/l, 54.8 mU/l and 52.5 mU/l in well-controlled subjects (p greater than 0.05). The mean increment in peak plasma glucose values for the three breakfasts was as follows: 6.9 mmol/l, 6.3 mmol/l and 6.2 mmol/l for the uncontrolled group against 7.2 mmol/l, 5.9 mmol/l and 6.2 mmol/l in well-controlled subjects; the mean increment in peak plasma insulin levels was 21.8 mU/l,22.0 mU/l and 24.2 mU/l in the controlled group versus 38.2 mU/l, 32.0 mU/l and 34.7 mU/l in the well-controlled subjects, all values being non-significantly different (p greater than 0.05). We conclude that, in acute conditions, simple sugars have no additional hyperglycaemic effect over an isoglucidic amount of bread in well-and in badly controlled Type 2 diabetic patients, even at breakfast.

Rarity of a marked "dawn phenomenon" in diabetic subjects treated by continuous subcutaneous insulin infusion.

We assessed the quality of overnight glycemic control and the frequency of the "dawn phenomenon" (nadir-0800 h glycemic increase) in 41 insulin-dependent diabetic patients treated by continuous subcutaneous insulin infusion (CSII). Mean plasma glucose levels were near-normal during the 24 h and, in particular, constant throughout the night. In a subset of six patients overnight plasma free insulin concentrations were also constant during CSII. The majority of profiles (88%) showed a glucose nadir from 2.0 to 5.9 mmol/L (most frequently at 0600 h) and had an 0800 h value from 2.0 to 6.9 mmol/L (92%). A large proportion (46%) of profiles showed a zero or negative nadir-0800 h glycemic increase. In 22 patients with three or more profiles recorded at the same basal insulin infusion rate, only one of 103 profiles had a fasting glycemic increase greater than an arbitrary value of 5.0 mmol/L (5.3), although many patients exhibited small dawn glycemic increases (e.g., 14 of 22 had a mean increase of from 0 to 2 mmol/L). In 12 subjects a 15% reduction in basal insulin infusion rate increased the mean +/- SEM dawn glycemic increase from 0.58 +/- 0.25 mmol/L to 2.7 +/- 0.76 mmol/L (P less than 0.025) as well as significantly increasing the nocturnal nadir and 0800 h plasma glucose concentrations. Thus, a marked dawn phenomenon is rare when a single but adequate basal infusion rate is used for CSII, and this questions the need in the majority of patients for preprogrammable pumps with nocturnal infusion rate changes.

Pancreas transplants from related donors.

Of 89 pancreas transplants performed at the University of Minnesota between July 1978, and March 1983, 36 have been segmental grafts from living-related donors (17 HLA-identical siblings, 6 identical twins, 13 HLA-mismatched relatives). All recipients had been diabetic for at least 10 years and all donors were at least 10 years older than the ages of onset of diabetes in the recipients; in the case of sibling donors, no other siblings or family members other than the recipient were diabetic. Changes in plasma glucose and serum insulin levels occurred in most donors postoperatively, but glucose tolerance tests usually remained normal. Of the 36 grafts from related donors, 16 are currently functioning (12 were technical failures), as compared with 10 of 53 from cadaver donors (10 were technical failures). The pancreatic ducts were left open, injected with synthetic polymers, or anastomosed to a Roux-en-Y limb of recipient jejunum. All techniques have been associated with successes and failures, but we currently prefer the enteric-drainage technique. The patient survival rates for recipients of transplants from related versus cadaver donors were 94% versus 78% (P less than .013); the respective graft survival rates were 43% versus 20% (P = .25). When only technically successful grafts were considered, the one-year function rates were 65% for pancreas grafts from related donors (n = 29) versus 25% for those from cadaver donors (n = 43) (P = .005). The highest success rate has been in azathioprine-treated recipients of technically successful pancreas transplants from related donors of a previous kidney (3 of 3 grafts from HLA-identical siblings and 3 of 3 from HLA-mismatched relatives are functioning). However, 7 of 9 technically successful grafts from HLA-identical siblings in nonuremic, non-kidney-transplant recipients treated with cyclosporine are also functioning (one-year graft survival rate of 76%). The results in nonuremic, non-kidney-transplant recipients of mismatched related grafts have not been so good, and only one of 5 technically successful grafts in this category is currently functioning. However, this patient has been treated with cyclosporine, azathioprine, and prednisone (triple therapy)--an immunosuppressive regimen we have recently applied with success in nonuremic, non-kidney-transplant recipients of cadaveric grafts.(ABSTRACT TRUNCATED AT 400 WORDS)

Aqueous humour glucose concentration in cataract patients and its effect on the lens

The glucose concentrations of the blood plasma and aqueous humour were measured in 56 cataract patients. The sodium concentration and colour of the lenses were determined after extraction. The mean plasma and aqueous glucose levels were 5·8 and 3·2 m m respectively in non-diabetic patients, while the values for diabetics were 14·2 and 7·8 m m. The sodium concentration of the lenses from non-diabetic patients appeared to consist of two distributions around 30 and 170 m m, corresponding to nuclear and cortical cataracts respectively. Only two lenses from the non-diabetic patients had sodium concentrations in the range 60–120 m m. In diabetic patients, however, 80% of the extracted lenses had sodium concentrations in this intermediate range. The data indicate that the osmotic stresses induced in the lenses of diabetic and non-diabetic patients are different. The diabetic lenses were also distributed in the middle range when nuclear colour was graded on a scale from I to V, while normal lenses were again normally distributed at either end of the scale.

Insulin, glucagon, and somatostatin release from the prediabetic Chinese hamster.

Diabetes mellitus in the adult Chinese hamster is characterized by subnormal pancreatic insulin release in vitro, decreased insulin content, and lack of obesity. The cause of the islet B-cell failure is not clear. We measured insulin, glucagon, and somatostatin release from in vitro perfused pancreases of young (mean age 10 and 20 weeks), genetically diabetic animals (subline AC, mean plasma glucose 8.0 and 16.6 mmol/l, respectively). Compared to age- and sex-matched normal hamsters (subline M, mean plasma glucose 5.3 mmol/l), the younger diabetic animals had a significantly elevated mean plasma glucose level, but net in vitro pancreatic release of insulin, glucagon, and somatostatin was normal. Pancreatic content of insulin and glucagon was also not significantly different from normal. At age 20 weeks, when the plasma glucose of the diabetic animals was even more elevated, pancreatic content and release of insulin were significantly subnormal, whereas glucagon and somatostatin release were normal, and pancreatic content of glucagon was normal. In a similar group of young (mean age 10 weeks) diabetic animals, non-fasting plasma insulin levels were within the normal range, but the corresponding glucose levels were excessive in most of the animals (13 out of 19). In conclusion, 10-week-old diabetic hamsters show mild hyperglycaemia which cannot be accounted for directly by decreased pancreatic release in response to a glucose plus arginine stimulus in vitro. Decreased ability of the B cell to respond in vivo to hyperglycaemia or peripheral resistance to insulin may contribute to later B-cell failure in the older diabetic hamster.

Plasma glucose and insulin responses in growing rats fed a total parenteral nutrition diet either intravenously or intragastrically.

The effect of administering either intravenously (group I) or intragastrically (group II) a glucose-amino acid total parenteral nutrition diet over a 12-day period upon plasma glucose and insulin responses was examined in adolescent rats. Infusion of the 25% glucose - 12.2% amino acid diet at a rate of 300 kCal X kg body weight-1 X 24 h-1 supported normal weight gain over the 12-day study period in both intravenously (group I) and intragastrically (group II) alimented rats. Mean plasma glucose levels rose dramatically in both groups by the end of day 1; group I had significantly higher mean plasma insulin levels. By day 3, the group I mean plasma glucose value decreased significantly while the group II mean glucose value remained virtually unchanged. Mean plasma insulin values more than doubled in both groups with the group I level still remaining significantly above the group II level. At days 6 and 12, group I mean plasma glucose levels were significantly below group II while both groups had similar plasma insulin levels. Data from this 12-day intravenous-intragastric alimentation study reveals quite different metabolic responses compared with acute (120-180 min) studies of the enteroinsular axis.

Threshold effect of plasma glucose in the glomerular hyperfiltration of diabetes.

Glomerular filtration rate (GFR) is abnormally high in some, but not all, insulin-dependent diabetic patients. The potential importance of this hyperfiltration lies in its possible link with later severe diabetic kidney disease. Inadequate glycaemic control is closely related to hyperfiltration but the mechanisms of the association are obscure. GFR and prevailing plasma glucose concentration were examined in a group of insulin-dependent diabetics without clinical proteinuria and in a group of non-diabetics, and their relationships observed using linear and multiple regression analysis. A positive correlation (r = 0.30, p less than 0.05) is found between mean plasma glucose concentration and GFR up to a mean plasma glucose level of approximately 13.5 mmol/l. Glycaemia in excess of this degree tends to be associated with a lower GFR. Multiple regression analysis confirmed the independence of plasma glucose as a determinant of GFR (p less than 0.05) at concentrations below 13.5 mmol/l. GFR declined significantly with age, but independently of diabetes duration, in the diabetic group (r = -0.48, p less than 0.001). GFR in the control group showed a statistically non-significant decline with age.

Effect of Acarbose on Blood Glucose Profile of Totally Insulin-Dependent Diabetic Patients

SummaryThe effects of an a-glucosidase inhibitor, Acarbose (Bay g 5421) upon the circadian plasma glucose profile were studied in 7 diabetic patients in i hospital. All subjects were totally insulin-dependent as demonstrated by their low preand postprandial plasma C-peptide levels. The patients received Acarbose (5 days) or a placebo (4 days) in a randomized order.The mean plasma glucose levels, the M value and the MAGE index recorded during both periods were compared. Acarbose was given at doses of 200, 100 and 100 mg before breakfast, lunch and dinner, respectively. The doses of regular insulin (4/day) were daily adapted throughout the study in an attempt to reach the best possible glycemic control. Even though the insulin doses did not significantly differ during both periods, a significant dei crease of the mean plasma glucose levels was observed when the patients received Acarbose (8.2 ± 0.4 vs 10.1 ± mmol/1; P < 0.05). Moreover, the drug induced a significant decrease of postprandial plasma glucose ...

Infection and Diabetes: The Case for Glucose Control

This review summarizes data concerning the host resistance to infection in diabetes and the influence of an acute infection upon the endocrinologic-metabolite status of the diabetic patient. While it is well known that acute infections lead to difficulty in controlling blood sugar levels and the infection is the most frequently documented cause of ketoacidosis, controversy persists as to whether or not patients with diabetes mellitus are more susceptible to infection than age- and sex-matched nondiabetic control subjects. Our data obtained from the charts of 241 diabetic patients who were being followed as outpatients show a striking direct correlation between the overall prevalence of infection (p less than 0.001) and the mean plasma glucose levels (representing three or more fasting glucose determinations taken at times when no evidence of infection existed). There is a significant diminution in intracellular bactericidal activity of leukocytes with Staphylococcus aureus and Escherichia coli in subjects with poorly controlled diabetes in comparison with the control group. Serum opsonic activity for both Staph. Aureus and E. coli were significantly lower than in the control subjects. Taken together, the results from published reports as well as our data suggest to us that good control of blood sugar in diabetic patients is a desirable goal in the prevention of certain infections (Candida vaginitis, for example) and to ensure maintenance of normal host defense mechanisms that determine resistance and response to infection.

Influence of Genetics and Diet on the Development of Diabetes in Yucatan Miniature Swine

The intent of this study was to examine the effect of a diet nutritionally similar to that consumed by most Americans on Yucatan miniature swine that have been bred for enhanced and impaired glucose tolerance. Seventeen Yucatan miniature pigs from the glucose-intolerant line (low K) and 17 from the glucose-tolerant line (high K) were selected. The oral glucose tolerance (OGT) of both groups of pigs was determined. After the OGT test (OGTT), 13 low K pigs and 12 high K pigs were placed on the American Swine Diet (ASD). The remaining animals were left on the regular swine diet. After 5 months, the pigs were again tested with an OGTT. Mean plasma glucose levels observed during the OGTT showed significant differences between the low K and high K groups on ASD at all time intervals from 60 to 150 minutes postdosing. Serum insulin levels in the high K group were significantly elevated over those in the low K group during the OGTT at 10, 20, and 30 minutes prediet, and at 10 minutes after 5 months on diet. Both low and high K groups showed a dietary effect with an elevated plasma glucose response to an OGTT, although the mean increase was not significant in the high K group. In the low K group, plasma glucose levels were significantly elevated (P < 0.05) over prediet values at 20, 30, 60, 90 and 120 minutes. In addition, 7 out of the 10 low K pigs tested at 5 months developed insulin resistance, and noninsulin-dependent diabetes.diabetes diet miniature swine genetics

Lipid Metabolism in Non-Insulin-Dependent Diabetes Mellitus

Plasma lipid concentration and lipoprotein composition were studied before and after several months of glipizide treatment in 23 patients with non-insulin-dependent diabetes mellitus. The mean (+/- SEM) plasma glucose level fell 87 mg/dL, and the fall in plasma glucose concentration was correlated with a reduction in plasma triglyceride, very low-density lipoprotein triglyceride, cholesterol, and low-density lipoprotein cholesterol levels. Furthermore, there was a statistically significant increase in the plasma high-density lipoprotein cholesterol to total cholesterol ratio. Thus, improved diabetic control in patients treated with glipizide with non-insulin-dependent diabetes mellitus leads to changes in lipoprotein metabolism thought to be beneficial in terms of known cardiovascular risk factors.

Glycemic control in insulin-dependent diabetes mellitus: Comparison of outpatient intensified conventional therapy with continuous subcutaneous insulin infusion

We compared glycemic control achieved on an outpatient basis with three insulin regimens in 10 patients with insulin-dependent diabetes mellitus. The regimens studied included: (1) intensified conventional therapy with twice-daily regular and lente insulin; (2) intensified conventional therapy with long-acting ultralente insulin plus multiple preprandial injections of regular insulin; (3) continuous subcutaneous insulin infusion. Each treatment period was two months long. At the beginning of the study and the close of each study period, patients were hospitalized for a 48-hour evaluation of glycemic control. Each new insulin regimen was begun after discharge, with the dosage adjusted using preplanned algorithms, patient self-monitoring of blood glucose and defined blood glucose targets. Glycemic control markedly improved on all three treatment regimens, to a comparable degree, as assessed by mean plasma glucose level, mean amplitude of glycemic excursions, M value (an index of glycemic lability), urinary glucose excretion and glycosylated hemoglobin level.

Effect of cyclosporin A on allotransplanted pancreatic fragments to the spleen of totally pancreatectomized dogs.

Cyclosporin A (Cy A) was evaluated in dogs to assess its effectiveness of prolonging survival of allogeneic pancreatic islet tissue transplanted to the spleens of totally pancreatectomized mongrel dogs. Thirty-seven dogs were made diabetic by total pancreatectomy. Ten untreated pancreatectomized animals survived a mean (+/-SE) of 6.3 +/- 0.9 days and died with mean (+/-SE) plasma glucose levels of 23.2 +/- 2.7 mmol/liter. Dispersed pancreatic fragments, prepared by collagenase digestion without separation of exocrine and endocrine components, were directly implanted into the splenic pulp of 27 pancreatectomized dogs. Twelve dogs given autotransplants became normoglycemic after 4.3 +/- 0.5 days and remained so until killed at 60 days post-transplant, although normal glucose tolerance tests were not achieved. Eight nonimmunosuppressed dogs given allogeneic pancreatic fragments did not become normoglycemic but survived for 13.0 +/- 2.1 days, the dogs dying with a terminal plasma glucose of 22.7 mmol/liter. An additional seven dogs given allogeneic transplants were given Cy A (oral solution), 25 mg/kg/day, for 14 days, and, although failing to become normoglycemic, survived for 28.1 +/- 5.4 days and died with terminal plasma glucose levels of 25.1 +/- 0.6 mmol/liter. Intrasplenic complications included subcapsular hematomas, intrasplenic necrosis and cavitation, capsular perforations, and arteriolar thrombosis. The failure to achieve normoglycemia with allogeneic dispersed pancreatic tissue in dogs treated with Cy A and the complications associated with the implantation of the tissue in the spleen do not suggest that this approach is worthy of clinical trial.

Idiopathic leucine-sensitive hypoglycemia syndrome: insulin and glucagon responses and effects of diazoxide.

Four children, treated with diazoxide for idiopathic leucine-sensitive (ILS) hypoglycemia of infancy, had follow-up studies at 2 to 10 yr of age to assess: (1) persistence of leucine sensitivity in later childhood. (2) pancreatic glucagon responses, and (3) the hormonal and glycemic effects of diazoxide therapy. On the third day after diazoxide therapy was stopped, the mean +/- S.E. baseline plasma glucose level (65.3 +/- 3.4 mg/dl) was significantly (P less than 0.005) lower than that of the controls (80.1 +/- 3.1 mg/dl). Corresponding mean plasma immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) values were higher than control values but the differences were not significant. After the oral administration of leucine (50 mg/kg) in the ILS children, the mean plasma IRI level rose from 15.2 +/- 4.1 to 59 +/- micro U/ml, the mean plasma glucose concentration fell to 36.0 +/- 3.3 mg/dl and the mean plasma IRG level rose from 196 +/- 16 to 261 +/- 41 pg/ml. These responses were significantly greater (P less than 0.05 to 0.005) than those of control children who received 150 mg/kg of leucine. Intravenous arginine administration caused similar changes in mean plasma glucose, IRI and IRG values in the ILS and control children. During diazoxide therapy in the ILS children, the baseline mean plasma glucose level (89.5 +/- 4.2 mg/dl) was significantly (P greater than 0.005) higher than without therapy. Corresponding mean plasma IRI and IRG values decreased with therapy but the differences were not significant. Diazoxide therapy blunted the changes induced by leucine administration in the ILS children but did not significantly change their response to arginine infusion. Our results indicate that marked sensitivity to leucine persists after infancy in the ILS children. Their IRG responses are appropriate to the stimuli, indicating that their pancreatic alpha cells do not share the abnormality of the beta cells. Diazoxide therapy increases baseline plasma glucose levels and inhibits IRI responses to leucine in ILS children, but it has little if any effect on IRG responses.

Continuous subcutaneous insulin infusion at home: apropos of 3 cases

SummaryContinuous subcutaneous insulin infusion (CSII) was performed in 3 totally insulin dependent diabetic patients (postprandial C peptide: 0.03 ± 0.01 pmol/l) for periods lasting up to 9 months. During this period, each patient measured his capillary blood glucose 2 to 5 times per day with the Dextrosix(R)/Dextrometer(R) method. A good glycemic control was achieved at home, as assessed by a mean plasma glucose level of ± 140 mg/dl and a M value ranging from 9 to 24. The mean total glycosylated hemoglobin levels in the 3 patients were 9.3, 9.2 and 11.9% respectively. Hypoglycemic episodes were rarely observed; CSII did not affect the usual way of life of the patients. We did not observe any improvement of the conduction velocy of sciatic nerves, as assessed by electro-myography after a few months of CSII.We conclude that a good glycemic profile can be obtained at home in totally insulin dependent patients with CSII.

Intermittent hyperinsulinaemia and arterial glycosaminoglycans in dogs

The effect of insulin on the glycosaminoglycan content of the arterial ground substance was compared in age-matched alloxan-diabetic dogs, hypophysectomized dogs and normal controls. Hyaluronic acid and the three sulphated components, heparan, dermatan and isomeric chondroitin sulphates were quantitatively determined in the arch, thoracic and abdominal aorta, and in the carotid, coronary, iliac, renal and mesenteric arteries. Diabetic animals were either well or poorly controlled. Six well controlled dogs with a fasting mean plasma glucose level of 8.5 mmol/l were given around 30 units of porcine insulin/day and showed fluctuations in plasma insulin concentrations between 24 and 175 mU/l. Four poorly controlled dogs with a mean fasting plasma glucose level of 18.5 mmol/l received an average of 14 units of insulin/day, and the fluctuations ranged from 8 to 113 mU/l. Eight normal, untreated controls showed mean fluctuations between 15 and 22 mU/l. Within 14 weeks of insulin treatment, well controlled animals displayed glycosaminoglycan alterations in five arterial segments, usually involving more than one glycosaminoglycan constituent. In poorly controlled animals the number of segments that showed glycosaminoglycan alterations was the same, but abnormalities were limited to one of the sulphated components only. The coronary arteries displayed identical glycosaminoglycan alterations in the two groups of diabetic dogs, namely a significant rise in dermatan sulphate content (p < 0.01, mean±SEM) from the normal value of 1.12±0.03 mg/g dry defatted tissue to 1.31±0.03 mg/g in well controlled animals and to 1.37±0.08 mg/g in poorly controlled animals. In order to ascertain that the abnormalities in the glycosaminoglycan chemistry were related to hyperinsulinaemia rather than hyperglycaemia, six hypophysectomized dogs were treated with 1.5 U/day of porcine protamine zinc insulin, for 3 weeks. Average plasma glucose levels were in the order of 4.3 mmol/l and plasma insulin levels fluctuated between 9 and 27 mU/l; the latter represented twice the peak value seen in five untreated hypophysectomized dogs. The resulting chemical changes in the glycosaminoglycan content were in line with those encountered in diabetic animals, including the rise in dermatan sulphate content of the coronary arteries. These results indicate that: (1) hyperinsulinaemia produced by injections of insulin causes alterations of the arterial glycosaminoglycan content; (2) not all segments of the arterial tree are equally responsive to insulin and (3) the coronary arteries have a particularly insulin-sensitive dermatan sulphate metabolism.

Urinary excretion and renal clearance of specific plasma proteins in diabetes of short and long duration.

To characterize the renal handling of protein in diabetics, the 24-h total protein excretion (Shevky-Stafford method), as well as urinary excretion, plasma concentration, and clearance of each of 17 proteins (radial immunodiffusion technique) were determined in 25 nondiabetic and 31 diabetic Pima Indians and in 25 nondiabetic Caucasians. Determination of 24-h total protein excretion demonstrated similar levels in nondiabetic Pimas [8.6 mg/24 h (median), 5.0-18.0 mg/24 h (95% confidence interval)] and nondiabetic Caucasians [10.1 mg/24 h, 7.0-24.0 mg/24 h] but significantly elevated levels in Pima diabetics [41.0 mg/24 h, 24.0-163.0 mg/24 h]. Total protein excretion was significantly greater among those with diabetes of 10 or more yr duration with retinopathy [163.0 mg/24 h, 24.0-436.0 mg/24 h] and those with recent onset of diabetes [39.5 mg/24 h, 24.7-81.0 mg/24 h], whereas long-duration diabetics without retinopathy [11.5 mg/24 h, 6.7-29.0 mg/24 h] and nondiabetic Pimas had similar values. Mean blood pressure and fasting plasma glucose levels were positively correlated with total protein excretion in the diabetic Pimas. Measurable quantities of only 9 of the 17 individual proteins were detected in the urine in more than 50% of all nondiabetic and diabetic subjects. They were β2- microglobulin, β2-glycoprotein I, α1-acid glycoprotein, α2 HS-glycoprotein, α1-antitrypsin, albumin, hemopexin, transferrin, and IgG. The excretions and clearances ofthese proteins were comparable in nondiabetic Pimas and Caucasians. Compared with nondiabetic Pimas, diabetics had significantly higher clearance and excretion of each of these proteins, except β2-microglobulin (mol. wt. = 11,600) and α-glycoprotein I (mol.wt. = 40,000). Long-duration diabetics with retinopathy and recent-onset diabetics both had significantly elevated clearance and excretion of the same proteins. In contrast, long-duration diabetics without retinopathy had significant increases of clearance and excretion only of hemopexin, transferrin, and IgG. The IgG/transferrin clearance ratios were not significantly different among the nondiabetic and diabetic groups. The other eight proteins were detected in the urine in measurable quantities in less than 50% of all subjects. These were prealbumin, gc-globulin, antithrombin III, plasminogen, haptoglobin, C3 activator, C4- component, and C3-component. While for statistical reasons, clearance data could not be analyzed for these proteins, a significantly higher percentage of diabetic Pimas had detectable excretion of these proteins except for C3 activator. In conclusion, diabetics, even of recent onset, have increased urinary excretion and clearance of proteins with a molecular weight greater than 40,000 compared with nondiabetics. This increased glomerular permeability appears to be nonselective for the larger proteins and can be detected shortly after the onset of diabetes. It might be predictive of the development of more severe renal disease after longer duration of diabetes.