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Biomedical subjects

S N Davis

Publications and source records attributed to S N Davis.

At least 55 records · Page 3Linked to original sources
PubMed1993

The effects of differing insulin levels on the hormonal and metabolic response to equivalent hypoglycemia in normal humans.

The aim of this study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent hypoglycemia in normal humans. Experiments were conducted in 9 normal, lean men, who had fasted overnight. Insulin was infused in two separate, randomized protocols so that steady-state levels of 486 +/- 33 (low) and 3056 +/- 236 pM (high) were obtained. Glucose was infused during both protocols to ensure that the rate of fall of plasma glucose (0.07 mM/min) and hypoglycemic plateau (2.8 +/- 0.1 mM) were similar. Despite similar plasma glucose levels, EPI (8.7 +/- 0.7 vs. 5.5 +/- 0.7 nM), NE (3.3 +/- 0.3 vs. 2.3 +/- 0.2 nM), and cortisol (811 +/- 36 vs. 611 +/- 72 nM) significantly increased during high compared with low insulin infusion, respectively (P < 0.05). Glucagon, growth hormone, and pancreatic polypeptide levels increased briskly and significantly but were not different during the two insulin infusions. HGP rose significantly from 12.1 +/- 0.3 to 18.1 +/- 1.1 mumol.kg-1 x min-1 in response to the high insulin level (P < 0.05) but remained unchanged (12.1 +/- 0.4 and 11.7 +/- 1.4 mumol.kg-1 x min-1) in the presence of th low insulin level. GRa increased significantly during high insulin levels (3.4 +/- 0.3 to 4.8 +/- 0.7 mumol.kg-1 x min-1, P < 0.05) but remained at a basal rate (3.0 +/- 0.3 to 2.7 +/- 0.6 mumol.kg-1 x min-1) in the presence of low insulin levels. sBP and heart rate increased more during high insulin infusion (18 +/- 5 vs. 6 +/- 5 mmHg and 18 +/- 4 vs. 7 +/- 2 beats/min, respectively, P < 0.05). In summary, the 6-fold higher insulin level resulted in significantly greater increases in catecholamine and cortisol secretion, HGP, lipolysis, heart rate, and sBP despite equivalent hypoglycemia. We conclude that at moderate hypoglycemia, high doses of insulin can augment certain aspects of the counterregulatory response in normal humans.

Adult↗
PubMed1993

Counterregulation during hypoglycemia is directed by widespread brain regions.

Previous studies have demonstrated the importance of the brain in directing counterregulation during insulin-induced hypoglycemia in dogs. The capability of selective carotid or vertebrobasilar hypoglycemia in triggering counterregulation was assessed in this study using overnight-fasted dogs. Insulin (21 pM.kg-1.min-1) was infused for 3 h to create peripheral hypoglycemia in the presence of 1) selective carotid hypoglycemia (vertebral glucose infusion, n = 5), 2) selective vertebrobasilar hypoglycemia (carotid glucose infusion, n = 5), 3) the absence of brain hypoglycemia (carotid and vertebral glucose infusion, n = 4), or 4) total brain hypoglycemia (no head glucose infusion, n = 5). Glucose was infused via a leg vein as needed in each group to minimize the differences in peripheral glucose levels (2.6 +/- 0.1, 3.0 +/- 0.2, 2.7 +/- 0.1, and 2.5 +/- 0.1 mM, respectively). The humoral responses (cortisol, glucagon, catecholamines, and pancreatic polypeptide) to hypoglycemia were minimally attenuated (< 40%) by selective carotid or vertebrobasilar euglycemia. In addition, the increase in hepatic glucose production, as assessed using [3-3H]glucose, was attenuated by only 41 and 34%, respectively, during selective carotid or vertebrobasilar hypoglycemia. These observations offer support for the hypothesis that more than one center is important in hypoglycemic counterregulation in the dog and that they are located in brain regions supplied by the carotid and vertebrobasilar arteries, because significant counterregulation occurred when hypoglycemia developed in either of these circulations. Counterregulation during hypoglycemia, therefore, is probably directed by widespread brain regions that contain glucose-sensitive neurons such that the sensing sites are redundant.

Animals↗
PubMed1993

Estimates of insulin action in normal, obese and NIDDM man: comparison of insulin and glucose infusion test, CIGMA, minimal model and glucose clamp techniques.

Many methods of varying complexity are available for the measurement of insulin resistance (action) in man. No study has previously compared several of these in the same subjects to establish which is the most appropriate for routine use. We have, therefore, compared six methods: the hyperinsulinemic eu(iso)-glycaemic clamp (Eu), insulin glucose infusion test (IGI), hyperglycaemic clamp (Hy), continuous infusion of glucose with model assessment (CIGMA), minimal model (Min) and modified minimal model (Mod). Nineteen subjects with varying degrees of glucose tolerance were studied. Eight normal (BMI 22.5 +/- 1.5 kg/m2), six obese (BMI 38 +/- 5 kg/m2) and five NIDDM subjects (BMI 27 +/- 3 kg/m2) were investigated, in a randomized fashion, on separate days. The ratio of metabolic clearance rate of glucose (MCRG) and Insulin (I) was used as the measure of insulin action during Eu, Hy and IGI. Si was calculated as the index of insulin sensitivity from (Min) and (Mod) and CIGMA was obtained as previously described. MCRG was converted to Si to allow for direct comparison with (Min). Methods requiring incremental endogenous insulin secretion (which was highly variable) to calculate an index of insulin action (Si Min, Si Hy and CIGMA) failed to find an overall difference between groups. Only Si Eu (p = 0.007) and Si IGI (p = 0.001) demonstrated a significant overall group difference when Si was used. When MCRG/I was used, Eu, IGI and Hy were able to distinguish a significant overall group difference. With the exception of CIGMA and SiHy all other methods found a significant difference in insulin action between normals and NIDDM subjects. Only Eu and IGI could distinguish obese from normal, while only Si Min, could distinguish obese from NIDDM subjects. Eu and IGI were the only methods to be significantly correlated: normals Rs = 0.75, p < 0.05, obese Rs = 0.9, p < 0.05, and NIDDM Rs = 1.0, p < 0.05. In conclusion we have demonstrated that: 1) The insulin-glucose infusion test and the eu(iso)glycaemic clamp were significantly correlated in normals, obese and NIDDM subjects. 2) Only the eu(iso)glycaemic clamp and insulin glucose infusion test could significantly separate obese from normal subjects. 3) the IGI appears to be a practical, simple and precise method for measuring in vivo insulin action in man and gives results closely similar to those found with the hyperinsulinemic eu(iso)glycaemic clamp.

Adult↗
PubMed1993

Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMTIA duplication.

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. One form of CMT, CMT type 1A, is characterized by uniformly decreased nerve conduction velocities, usually shows autosomal dominant inheritance, and is associated with a large submicroscopic duplication of the p11.2-p12 region of chromosome 17. A cohort of 75 unrelated patients diagnosed clinically with CMT and evaluated by electrophysiological methods were analyzed molecularly for the presence of the CMT1A DNA duplication. Three methodologies were used to assess the duplication: measurement of dosage differences between RFLP alleles, analysis of polymorphic (GT)n repeats, and detection of a junction fragment by pulsed-field gel electrophoresis. The CMT1A duplication was found in 68% of the 63 unrelated CMT patients with electrophysiological studies consistent with CMT type 1 (CMT1). The CMT1A duplication was detected as a de novo event in two CMT1 families. Twelve CMT patients who did not have decreased nerve conduction velocities consistent with a diagnosis of CMT type 2 (CMT2) were found not to have the CMT1A duplication. The most informative molecular method was the detection of the CMT1A duplication-specific junction fragment. Given the high frequency of the CMT1A duplication in CMT patients and the high frequency of new mutations, we conclude that a molecular test for the CMT1A DNA duplication is very useful in the differential diagnosis of patients with peripheral neuropathies.

Charcot-Marie-Tooth Disease↗
PubMed1993

The hormonal and metabolic responses to prolonged hypoglycemia.

The purpose of this review was to summarize some of the recent advances that have been made in the understanding of the physiology involved in the counter-regulatory response to prolonged hypoglycemia. It is hoped that this review may stimulate thought and increase awareness that other factors, in addition to the glycemic level, can affect the counterregulatory response. However, if the goal of tight metabolic control is to be achieved in subjects with diabetes, the spectre of severe hypoglycemia must be removed. Thus further work is needed to understand the physiologic mechanisms controlling hypoglycemic counterregulation in normal subjects and the syndromes of abnormal counterregulatory responses present in subjects with IDDM.

Animals↗
PubMed1992

Dose-response characteristics of human proinsulin and insulin in non-insulin-dependent diabetic humans.

We compared the actions of human proinsulin and insulin on glucose turnover and on intermediary carbohydrate and lipid metabolism in non-insulin-dependent diabetes mellitus (NIDDM). Six diet-controlled weight-matched (25.4 +/- 1.0 kg/m2) NIDDM subjects underwent six separate isoglycemic clamps. Glucose turnover was measured using a primed continuous infusion of [6',6'-2H2]glucose. Each subject received three low-dose intravenous infusions of both insulin and proinsulin. Blood glucose was maintained at 6.7 +/- 0.3 mM during proinsulin and insulin infusion. Insulin (I) infusions gave steady-state levels of 0.12 +/- 0.001 (I1), 0.18 +/- 0.01 (I2), and 0.33 +/- 0.01 nM (I3). Steady-state proinsulin (P) levels were 2.5 +/- 0.1 (P1), 4.3 +/- 0.2 (P2), and 8.8 +/- 0.9 nM (P3). Hepatic glucose production was suppressed equally by proinsulin and insulin at all doses. The metabolic clearance rate of glucose was significantly increased during the insulin infusion compared with proinsulin. The use of [6',6'-2H2]glucose resulted in a mean underestimation of the glucose infusion rate of 10.0 +/- 4.0 and 6.0 +/- 2.5% during the two highest insulin and proinsulin doses, respectively. Proinsulin had a significantly weaker effect than insulin, at the lowest infusion dose, in percent suppression of plasma nonesterified fatty acids, blood glycerol, and beta-hydroxybutyrate levels (all P less than 0.05). Blood lactate levels were lower during the P1 (628 +/- 43 microM) and P2 (657 +/- 93 microM) infusions compared with I1 (776 +/- 60 microM) and I2 (878 +/- 44 microM; P less than 0.05, P less than 0.02), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1992

Effects of differing insulin levels on response to equivalent hypoglycemia in conscious dogs.

The aim of this study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent hypoglycemia. Insulin was infused intraportally into normal 18-h-fasted conscious dogs at 2 (low, n = 6) or 8 mU.kg-1.min-1 (high, n = 7) on separate occasions. This resulted in steady-state arterial insulin levels of 80 +/- 8 and 610 +/- 55 microU/ml, respectively. Glucose was infused during the high dose to maintain plasma glucose similar to low (50 +/- 1 mg/dl). Despite similar plasma glucose levels, epinephrine (2,589 +/- 260, 806 +/- 180 pg/ml), norepinephrine (535 +/- 60, 303 +/- 55 pg/ml), cortisol (12.1 +/- 1.5, 5.8 +/- 1.2 micrograms/dl), and pancreatic polypeptide (1,198 +/- 150, 598 +/- 250 pg/ml) were all increased in the presence of high-dose insulin (P < 0.05). Glucagon levels were similar during both insulin infusions. Hepatic glucose production, measured with [3-3H]-glucose, rose from 2.6 +/- 0.2 to 4.7 +/- 0.3 mg.kg-1.min-1 in response to high insulin (P < 0.01) but remained unchanged, 3.0 +/- 0.5 mg.kg-1.min-1, during low-dose infusions. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. By the final hour of the high-dose euglycemic clamps, cortisol (2.4 +/- 0.4 to 4.8 +/- 0.8 micrograms/dl) and norepinephrine (125 +/- 34 to 278 +/- 60 pg/ml) had increased (P < 0.05) compared with baseline. Plasma epinephrine levels remained unchanged during both series of euglycemic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of human proinsulin on glucose turnover and intermediary metabolism in insulin-dependent-diabetes mellitus.

We have compared the action of human proinsulin and insulin on glucose turnover, intermediary carbohydrate, and lipid metabolism in insulin-dependent-diabetic (IDDM) subjects. Six, young, weight-matched (23 +/- 2 kg-2) IDDM subjects underwent separate hyperinsulinemic euglycemic clamps. Three, low dose, iv infusions of both insulin and proinsulin were used to construct dose response curves. The proinsulin infusions were chosen to give steady state levels approximately or equal to 20-fold higher on a molar basis than insulin, based on previous findings that proinsulin has only 5-10% the biological potency of insulin. Hepatic glucose production, measured using [6'6'2H2]glucose, was suppressed equally by proinsulin and insulin at the three dose levels; (I1) 2.8 +/- 0.7 (P1) 3.3 +/- 0.6, (I2) 2.3 +/- 0.9 (P2) 3.3 +/- 1.1, (I3) -2.0 +/- 1.7 (P3) -1.1 +/- 0.6 mumol/kg min-1. Percentage elevation of glucose disposal was significantly increased during the insulin infusions compared to proinsulin; (I1) 132 +/- 12 (P1) 78 +/- 4 p < 0.01; (I2) 157 +/- 18 (P2) 104 +/- 14; P < 0.05; (I3) 242 +/- 23 (P3) 159 +/- 24 p = 0.02. Dose response curve analysis demonstrated that proinsulin stimulated glucose disposal approximately or equal to 3.7% whereas suppression of HGP was congruent to 5.7% compared to insulin. Proinsulin had a significantly weaker effect than insulin, at the lowest infusion dose, in percent suppression of plasma nonesterified fatty acids (I1 34 +/- 4, P1 14 +/- 15%; P < 0.05), blood glycerol (I1 47 +/- 4, P1 30 +/- 3%; P < 0.01) and 3-hydroxybutyrate levels (I1 81 +/- 7, P1 42 +/- 17%; P < 0.05). Proinsulin caused significant net reductions in blood lactate levels compared to insulin at each infusion dose; (P1) -130 +/- 34, (I1) -32 +/- 30 mumol/L (P < 0.05) (P2) -139 +/- 76 (I2) +8 +/- 65 mumol/L (P < 0.05) (P3) 48 +/- 60 (I3) 230 +/- 64 mumol/L (P < 0.05). We conclude that in IDDM: 1) proinsulin has a preferential effect on the liver compared to muscle, in terms of glucose handling; 2) proinsulin may have a different effect on lactate metabolism compared to insulin; 3) proinsulin at the lowest dose resulted in an inability to suppress lipolysis and ketogenesis; 4) glucose turnover can be underestimated using [6'6'2H2]glucose.

Adult↗
PubMed1992

Effects of human insulin on insulin binding antibody production in nondiabetic subjects.

OBJECTIVE: To test the hypothesis that human insulin may have a low immunogenicity and that short-term exposure may not cause endogenous insulin antibody production. RESEARCH DESIGN AND METHODS: Randomized double-blind prospective study. Serum samples collected for insulin binding antibodies and measured by a sensitive immunochemical assay. Subjects were seven healthy nondiabetic patients who had never received exogenous insulin. Each subject received 6 separate monthly injections of human insulin. On four occasions, both regular and NPH insulin were administered. On the other two occasions, either NPH or regular insulin was administered alone. RESULTS: Mean +/- SE basal insulin antibody levels (1.2 +/- 0.2 micrograms/L) increased to a maximal level of 4.5 +/- 0.8 micrograms/L after four injections. Thereafter, antibody levels declined to an end-of-study value of 2.5 +/- 0.3 micrograms/L. This represented a highly significant overall increase (P less than 0.001). A control group of six insulin-dependent diabetic subjects treated with human insulin over the same period as the test subjects demonstrated no change in insulin antibody concentrations (2.8 +/- 0.7-2.7 +/- 0.6 micrograms/L). CONCLUSIONS: These results suggest that human insulin preparations, when administered subcutaneously, may be more immunogenic than previously considered. The antigenic response was rapid, because only four subcutaneous injections were sufficient to produce insulin antibody levels in nondiabetic patients similar to those observed in insulin-dependent diabetic patients receiving chronic insulin replacement therapy.

Adult↗
PubMed1992

A comparison of four methods for assessing in vivo beta-cell function in normal, obese and non-insulin-dependent diabetic man.

Several methods of varying complexity are available for the measurement of in vivo insulin secretion in man. No study has previously compared these in the same subjects to establish which is the most appropriate for routine use. We have, therefore, compared four methods for measuring insulin secretion in man: Hyperglycaemic clamp (Hy), Minimal model (MIN), shortened intravenous glucose tolerance test (IVGTT) and continuous infusion of glucose with model assessment (C.I.G.M.A.). Seventeen subjects with varying degrees of insulin sensitivity were studied. Seven normal (BMI 22.5 +/- 1.5 kg/m2), five obese (BMI 38 +/- 5 kg/m2) and five NIDDM subjects (BMI 27 +/- 3 kg/m2) were investigated, in a randomised fashion, on separate days. First (PSI) and second phase (PSII) rate constants (MIN); incremental insulin secretion 0-10 mins (Hy delta I) and steady state insulin levels from the last 30 minutes (Hy120-150) from the hyperglycaemic clamp; 3 minute insulin concentration and incremental area under insulin secretion curve 0-10 min (IVGTT) and beta-cell function (%) from C.I.G.M.A. were used as indicators of insulin secretion. Each index of insulin secretion could detect an overall difference between the groups. Insulin secretion in normals and obese was similar but significantly increased compared to NIDDM. In normals PSI correlated with C.I.G.M.A. (Rs = 0.92, p < 0.02) and Hy120-150 (Rs = 0.82, p < 0.05). IVGTT0-10 correlated with PSII (Rs = 0.83, p < 0.05), HY delta I (Rs = 0.84, p < 0.05) and IVGTT3 min (Rs = 1.0, p < 0.001). In obese PSII correlated with C.I.G.M.A. (Rs = 0.91, p < 0.05), Hy delta I (Rs = 1.0, p < 0.02) Hy120-150 (Rs = 0.92, p < 0.05) and IVGTT3 min Rs = 1.0, p < 0.02). In addition Hy delta I also correlated with C.I.G.M.A. (Rs = 0.92, p < 0.05) and IVGTT3 min (Rs = 1.0, p < 0.02). In NIDDM Hy delta I correlated with C.I.G.M.A. (Rs = 0.91, p < 0.005). When all subjects from the three groups were combined, significant positive correlations were obtained between each index of insulin secretion. In conclusion we have demonstrated that: (a) C.I.G.M.A., IVGTT, Minimal model and hyperglycaemic clamp can provide similar overall results for, in vivo, beta-cell function in man. (b) Significant positive correlations were obtained between each index of insulin secretion when all subjects were combined. (c) Using the above methodologies insulin secretion in normal and obese appears similar but significantly increased compared to NIDDM subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

The effects of human proinsulin on glucose turnover and intermediary metabolism.

We compared the effects of human proinsulin and human insulin on glucose disposal, suppression of hepatic glucose production (HGP), and intermediary carbohydrate and lipid metabolism. Six young, lean, subjects underwent eight separate euglycemic clamps with low-dose intravenous (IV) infusions of insulin and proinsulin (four each). The insulin infusions gave steady-state levels of 0.08 +/- 0.004 (I1), 0.12 +/- 0.003 (I2), 0.18 +/- 0.07 (I3), and 0.25 +/- 0.06 nmol/L (I4). The proinsulin infusions were chosen to give steady-state levels approximately 20-fold higher on a molar basis than insulin, based on previous findings that proinsulin has only 5% to 10% the biological potency of insulin. Steady-state proinsulin levels were 1.2 +/- 0.04 (P1), 2.8 +/- 0.07 (P2), 4.5 +/- 0.3 (P3), and 6.9 +/- 0.3 nmol/L (P4). HGP was suppressed equally by proinsulin and insulin at the four dose levels. Percentage elevation of glucose disposal was significantly increased during each of the insulin infusions compared with proinsulin: I1 107% +/- 4%, P1 87% +/- 4% (P = .03); I2 143% +/- 7%, P2 125% +/- 12% (P = .01); I3 238% +/- 38%, P3 173% +/- 22% (P = .03); I4 283% +/- 17%, P4 178% +/- 11% (P = .002). Dose-response curve analysis demonstrated that proinsulin stimulated glucose disposal approximately 3.3% compared with insulin. The effectiveness of proinsulin in suppressing HGP was approximately 5% compared with insulin. Plasma nonesterified fatty acids, blood glycerol, and 3-hydroxybutyrate were suppressed by similar amounts during each of the four insulin and proinsulin doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A comparison of the pharmacokinetics and metabolic effects of human regular and NPH insulin mixtures.

The effects of three human premixes (Mixtard, Actraphane, Humulin M3), syringe mixed 30% regular and 70% NPH insulin, regular insulin alone and NPH insulin alone, on intermediary metabolism, plasma free insulin levels and action profiles were compared using the euglycemic clamp technique. Seven normal volunteers received 20 IU of each insulin subcutaneously in a randomized fashion on separate days. The first and last 60 min of the 6 h clamp were chosen as summary measures of clinical importance. Significantly elevated plasma free insulin levels were found with all treatments compared to NPH insulin alone during the first hour, although by the final hour only Mixtard produced significantly higher levels compared to NPH (19.4 +/- 1.2, 10.5 +/- 0.3 mU/l P less than 0.01, respectively). Analysis of area under the incremental insulin absorption curve demonstrated that Mixtard produced significantly increased levels compared to syringe-mixed regular: NPH (7.6 +/- 0.8), Actraphane (9.6 +/- 1.0) and Humulin M3 (9.0 +/- 0.8 mU/l all P less than 0.05). Mixtard also resulted in significantly higher glucose infusion rates compared to the other premixes. No difference in action was found between regular and pre- or syringe-mixed human insulins during the first hour of the studies. The effects on intermediary carbohydrate and lipid metabolism were similar for syringe and premixed insulins. We conclude that: (1) fixed human insulin mixtures with NPH cause no blunting of the action of the soluble component. (2) Actraphane and Humulin M3 are similar but Mixtard may have a greater effect on some aspects of insulin action. (3) In clinical practice, fixed human insulin mixtures will be as efficacious as syringe-mixed preparations but may be easier and more convenient to use.

Adult↗
PubMed1989

A comparison of human ultralente- and lente-based twice-daily injection regimens.

The problem of fasting hyperglycaemia remains unresolved on currently used twice-daily injection regimens. Human ultralente insulin is of longer duration than human lente and differs from it only in the nature of the zinc-insulin complex. In a 6-month double-blind crossover study these insulins were compared in 66 patients who were randomized to human ultralente or human lente insulin given together with human soluble insulin in a twice-daily injection regimen. Patients were seen monthly and crossed over after 3 months treatment. Fasting blood glucose concentrations on the ultralente regimen were considerably lower than on the lente regimen, the difference being statistically significant (6.6 +/- 0.5 vs 8.2 +/- 0.5 mmol l-1, p less than 0.05), but only present in those patients with fasting concentrations below the median. Glycosylated haemoglobin was identical on both regimens (9.3 +/- 0.2%). The evening ultralente dose was slightly but significantly lower than the evening lente dose (14.9 +/- 0.8 vs 15.5 +/- 0.8 U, p less than 0.05) thus endorsing the lowering effect of ultralente on the fasting blood glucose concentration. However, the incidence of serious hypoglycaemic events was higher on the ultralente regimen (0.38 +/- 0.10 vs 0.09 +/- 0.04 events per patient-month, p less than 0.02), the majority of nocturnal events occurring between 0500 h and breakfast. We conclude that ultralente insulin can give an improved fasting blood glucose concentration but that in those patients with more marked fasting hyperglycaemia or with a nocturnal hypoglycaemia problem it offers no clinical advantage over human lente insulin in a twice-daily injection regimen.

Adult↗
PubMed1989

Effect of blood glucose concentration on osmoregulation in diabetes mellitus.

Poorly controlled insulin-dependent diabetes mellitus is associated with considerable elevations of plasma vasopressin concentrations, although well-controlled diabetics have normal osmoregulated thirst and vasopressin release. We studied the effect of blood glucose concentration on osmoregulated thirst and vasopressin secretion in insulin-dependent diabetes mellitus. Blood glucose was maintained overnight, and for the duration of the study, in either the euglycemic (4-5 mmol/l) or hyperglycemic (10-12 mmol/l) range, and patients underwent infusion of hypertonic (855 mmol/l) sodium chloride solution. Plasma sodium was lower during the hyperglycemic study, but elevation in plasma sodium concentration by infusion of saline caused progressive linear increases in both thirst and plasma vasopressin concentrations in both studies. Linear regression analysis defined lowered plasma sodium thresholds for both thirst appreciation and vasopressin release during the hyperglycemic study, although the sensitivity of the osmoreceptors remained unchanged. Analysis of the data in terms of plasma osmolality, corrected for the increase in blood glucose in the hyperglycemic study, revealed no differences in the osmotic thresholds for thirst or vasopressin release; sensitivity of the osmoreceptors also remained the same. Drinking abolished thirst and lowered plasma vasopressin concentrations before major changes in plasma sodium were observed. These results show that insulin-dependent diabetic patients osmoregulate appropriately when moderately hyperglycemic but that the threshold plasma sodium for vasopressin secretion and thirst appreciation is lowered by an unknown mechanism.

Adult↗
PubMed1989

Double-blind crossover trial of isophane (NPH)- and lente-based insulin regimens.

Isophane (NPH) and lente insulin preparations have been the basis of insulin-injection regimens for many decades but were never formally compared. After a 2-mo run-in period, 82 patients were randomized to NPH (Protaphane) or lente (Monotard) insulin preparations given together with Actrapid as a twice-daily injection regimen in a double-blind study. Patients were seen monthly and crossed over after 5 mo of treatment. Control as assessed by glycosylated hemoglobin (NPH 9.2 +/- 0.1%, lente 9.3 +/- 0.1%, mean +/- SE) and fructosamine (1.55 +/- 0.02 and 1.57 +/- 0.02 mM) concentrations was identical for the two regimens as were home-collected laboratory-measured fasting blood glucose (BG) (NPH 8.8 +/- 0.5 mM, lente 9.0 +/- 0.5 mM) and mean BG (8.2 +/- 0.3 and 7.6 +/- 0.3 mM) concentrations. For both regimens, the major control problem was the BG concentration before and after breakfast. Total insulin dosage was similar (NPH 56.3 +/- 0.6 U/day, lente 57.2 +/- 0.6 U/day) with no tendency for a difference in the evening intermediate-acting dose (NPH 17.0 +/- 0.3 U/day, lente 17.0 +/- 0.3 U/day) to counter fasting hyperglycemia. Serum lipid concentrations and body weight confirmed the equivalence of control. Hypoglycemic events were recorded in personal diaries and graded by predetermined criteria. Self-treated, relative-assisted, and hospital/doctor-treated hypoglycemic events did not differ in frequency. We conclude that lente- and NPH-based twice-daily human insulin regimens give indistinguishable metabolic control.

Adult↗
PubMed1988

Osmoregulation of thirst and vasopressin secretion in insulin-dependent diabetes mellitus.

1. Osmotically stimulated thirst and vasopressin release were studied during infusions of hypertonic sodium chloride and hypertonic D-glucose in euglycaemic clamped diabetic patients and healthy controls. 2. Infusion of hypertonic sodium chloride caused similar elevations of plasma osmolality in diabetic patients (288.0 +/- 1.0 to 304.1 +/- 1.6 mosmol/kg, mean +/- SEM, P less than 0.001) and controls (288.6 +/- 0.9 to 305.7 +/- 0.6 mosmol/kg, P less than 0.001), accompanied by progressive increases in plasma vasopressin (diabetic patients, 0.9 +/- 0.3 to 7.7 +/- 1.5 pmol/l, P less than 0.001; controls 0.5 +/- 0.1 to 6.5 +/- 1.0 pmol/l, P less than 0.001) and thirst ratings (diabetic patients 1.0 +/- 0.2 to 7.1 +/- 0.5 cm, P less than 0.001; controls 1.8 +/- 0.4 to 8.0 +/- 0.5 cm, P less than 0.001) in both groups. 3. Drinking rapidly abolished thirst and vasopressin secretion before major changes in plasma osmolality occurred in both diabetic patients and healthy controls. 4. There were close and significant correlations between plasma vasopressin and plasma osmolality (diabetic patients, r = +0.89, controls r = +0.93) and between thirst and plasma osmolality (diabetic patients r = +0.95, controls r = +0.97) in both diabetic patients and healthy controls during hypertonic saline infusion. 5. Hypertonic D-glucose infusion caused similar elevations in blood glucose in diabetic patients (4.0 +/- 0.2 to 20.1 +/- 1.2 mmol/l, P less than 0.001) and healthy controls (4.3 +/- 0.1 to 19.3 +/- 1.2 mmol/l, P less than 0.001) but did not change plasma vasopressin or thirst ratings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗