Diagnostic confusion in diabetes with persistence of fetal haemoglobin.
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Adult↗
Biomedical subjects
P D Home
Publications and source records attributed to P D Home.
Is diabetes always diabetes?
Diabetes is always taken to be a life-long diagnosis. In order to re-examine this question, 75 g glucose tolerance tests (OGTT) were performed twice on 37 previously confirmed diabetic patients (mean duration of diabetes of 4.6 years; range 1-15 years) with normal glycosylated haemoglobin levels on regular review. Weight loss since institution of a healthy diet was 7.6 +/- 4.8 kg (+/- SE). Normal glucose tolerance was found in 27% of patients and impaired glucose tolerance in 21% with no significant change on rechallenge. HbA1 was 6.3 +/- 1.5% (+/- SD) (normal < 7.5%) in patients with normal glucose tolerance compared to 7.0 +/- 0.9% (+/- SD) in those with impaired glucose tolerance, P < 0.05. The response of the OGTT in these patients varied with dietary intake and weight. Such individuals could be regarded as having perfectly controlled diabetes or alternatively to have been cured. The definition of diabetes should be reviewed to allow people to escape the diagnosis where permanent change in dietary habits is established.
Blood Glucose↗
The effect of intraperitoneal insulin delivery on carbohydrate metabolism in type 1 (insulin-dependent) diabetic patients.
Patients with type 1 diabetes are usually given insulin subcutaneously, but this does not mimic the physiological route of pancreatic insulin release, which may be better achieved with intraperitoneal insulin. Five C-peptide negative type 1 diabetic patients were studied on two occasions, once with intravenous (IV) and once with intraperitoneal (IP) insulin. Normoglycaemia was maintained from 1700 h with variable insulin infusion, and glucose turnover and recycling assessed from 0600 to 0800 h. A 4-h hyperinsulinaemic (25 mU kg-1 h-1) euglycaemic clamp was then performed, with IP or IV insulin delivery. During the night similar insulin infusion rates were needed to achieve equal blood glucose concentrations. Glucose turnover was identical (IV: 2.4 +/- 0.2 vs IP: 2.3 +/- 0.1 mg kg-1 min-1) (+/- SE) with glucose/carbon recycling 8.8 +/- 4.7 and 12.8 +/- 2.9% (NS). Blood lactate, pyruvate and alanine concentrations were significantly higher with IP than IV insulin (P less than 0.05). During the clamp, insulin concentration was 28 +/- 3 mU/l with IV insulin and 15 +/- 1 mU/l with IP insulin (P less than 0.05) and glucose requirement 2.0 +/- 0.5 and 0.8 +/- 0.3 mg kg-1 min-1, respectively (P less than 0.05). Glucose carbon recycling was higher with IP insulin (P less than 0.05). We conclude that: (1) in type 1 (insulin-dependent) diabetic patients hepatic glucose production could be normalized with both routes of insulin administration, and (2) at the same insulin infusion rate, the relative peripheral hypoinsulinaemia with IP route is sufficient to increase the rate of release of gluconeogenic precursors, or decrease their hepatic uptake.
Adult↗
Twenty-four hour C-peptide and insulin secretion rates and diurnal profiles of glucose, lipids and intermediary metabolites in cirrhosis.
1. To examine the contributions of hypersecretion and decreased insulin clearance to the hyperinsulinaemia of cirrhosis, insulin secretion was calculated over the day from serum C-peptide concentrations and C-peptide metabolic clearance rate. The latter was measured during infusions of recombinant human C-peptide. In cirrhotic patients (n = 9) insulin secretion rate was twice that of normal control subjects (n = 10), both in the basal state [02.00-07.00 hours, 15.7 +/- 2.1 (mean +/- SEM) nmol/h (2.6 +/- 0.4 units/h) versus 7.0 +/- 0.9 nmol/h (1.2 +/- 0.2 units/h), P < 0.002] and over 24 h [787 +/- 93 nmol (132 +/- 16 units) versus 346 +/- 34 nmol (58 +/- 6 units), P < 0.001]. However, the area under the serum insulin concentration curve was approximately six times greater in the cirrhotic patients (24 h basal, 6.3 +/- 1.0 versus 1.1 +/- 0.3 nmol l-1 h, P < 0.001; 24 h total, 21.7 +/- 3.2 versus 3.7 +/- 0.7 nmol l-1 h, P < 0.001). Thus, despite impairment of insulin clearance there is continuing hypersecretion of insulin in cirrhosis. 2. The relationship of carbohydrate and lipid metabolism with insulin secretion was assessed. In cirrhotic patients, 24 h blood glucose profiles showed a worsening of glucose tolerance over breakfast, despite greater insulin secretion compared with other meals, suggesting that the insulin insensitivity of cirrhosis is worse at this time. 3. Cirrhotic patients showed impaired suppression of blood glycerol levels after meals but normal suppression of serum non-esterified fatty acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxybutyric Acid↗
Insulin injection site tissue depths and localization of a simulated insulin bolus using a novel air contrast ultrasonographic technique in insulin treated diabetic subjects.
Subcutaneous adipose tissue depth was measured in 50 randomly selected Type 1 diabetic patients by real-time ultrasound at five standard sites commonly used for injection. Tissue depths were often less than the length of the standard insulin syringe needle (12-13 mm) at the arm and thigh injection sites, especially in men. Thus, if the currently recommended perpendicular injection technique were to be employed, there would, in theory, be an appreciable risk of intramuscular insulin deposition. In order to determine the true site of deposition in those at risk (injection site tissue depth of < 12 mm), a novel air-contrast ultrasound imaging technique was developed. A mixture of 0.1 ml of air and 0.2 ml of sterile 0.9% saline was self-injected into an anterior thigh site by 30 subjects using their usual technique. The site of the resultant tissue depot was located by ultrasound. Sixty-three percent of the depots were localized to true subcutaneous tissue and the remaining 37% to between the fascial planes overlying muscle. None of the subjects proved to be injecting into muscle. These results contrast with predictions of the risk of intramuscular injection made from the ultrasound measurement of subcutaneous tissue alone at the anterior and lateral thigh sites of, respectively, 100 and 97% for men and 42 and 37% for women. Although 11 of the 30 subjects claimed to be using a full-depth perpendicular injection technique, on direct observation only four proved to be injecting perpendicularly and none of these to the full depth of the needle.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
A survey of lower limb amputation in diabetic patients.
A retrospective survey of non-traumatic and non-neoplastic lower limb amputations in Newcastle upon Tyne during 1989-91 was performed. Hospital data were cross-checked with the local limb fitting centre to ensure 100% ascertainment. The diabetic patients were found to be 39% of amputees and 42% of operations (all levels). Incidence of diabetes amputation was 5.7 per 100,000 population per year. Fifteen percent of the diabetic patients had diabetes first diagnosed when they were admitted for amputation. For the known diabetes patients, 46% were under diabetes care by general practitioners only. Forty-seven percent of the patients who were under the care of a hospital service for diabetes had incomplete foot examination and assessment. Mortality rate within 30 days after diabetic amputation was 10% and median life expectancy following amputation was 22 months. It seems likely that assessment and management of the diabetic foot remains suboptimal in Newcastle, and that protocols and audit of care could lead to improvements without additional resources.
Aged↗
Phrenic neuropathy in association with diabetes.
We report the case of a 51-year-old man who presented with breathlessness on exertion and orthopnoea in association with Type 2 diabetes mellitus. Investigation showed bilateral diaphragmatic paralysis due to phrenic neuropathy. There was no evidence of neuropathy or microvascular disease elsewhere. Phrenic neuropathy may be an important, albeit rare, complication of diabetes and diaphragmatic function should be considered in any patient with unexplained breathlessness and orthopnoea.
Diabetes Mellitus, Type 2↗
Autonomic function testing in diabetic subjects using sequential measurements.
The repeatability of commonly used electrocardiographic (ECG) related autonomic function tests was investigated in 25 diabetic subjects, mean age 44 (range 18-67) years and mean duration of diabetes 10 (< 1-35) years. Tests were based on deep breathing, the Valsalva manoeuvre, relaxed normal breathing, and standing up from a lying position. All tests were repeated twice at each session, with two sessions separated by a mean of 5 (range 3-8) months. ECG and respiratory data were recorded for subsequent analysis. Maximum (max) and minimum (min) RR intervals and instantaneous heart rate (HR) were determined. The mean and repeatability data (within-subject standard deviation) for 21 different test results were calculated, and included deep breathing sitting (max-min)RR 226 +/- 39 ms and (max-min)HR 19.3 +/- 3.2 beats min-1, Valsalva manoeuvre 1.74 +/- 0.18, and lying-to-standing RR ratio 1.19 +/- 0.07. The within-subject repeatability to between-subject variability ratios consistently demonstrated that it is better to perform the deep breathing test sitting (with the smaller mean ratio of 0.37) rather than supine (0.46), with the use of three respiratory cycles rather than a single cycle (0.33 compared with 0.50 for (max-min)RR). A significant (p = 0.037) relationship was found between variability in heart rate changes and variability in air volume breathed during the deep breathing test.
Adolescent↗
Repeatability of measurements and sources of variability in tests of cardiovascular autonomic function.
OBJECTIVE: To determine the repeatability and sources of variability of clinical tests of cardiovascular autonomic function. DESIGN: The commonly used electrocardiographic related tests of autonomic function were studied. Two repeat measurements of all tests were made on all subjects on four separate days over a four week period. SUBJECTS: Ten normal subjects with no known autonomic dysfunction were investigated. MAIN OUTCOME MEASURES: These were deep breathing (subject seated and supine), Valsalva manoeuvre, standing up from lying position, and normal relaxed breathing (subject supine). During the tests the electrocardiogram and respiratory pattern were recorded by computer. Beat to beat RR intervals were measured automatically from the electrocardiogram, and from these the results of the tests were calculated. RESULTS: Variance analysis showed significant between subject variability for all tests (p < 0.005), but some tests showed a much smaller relative within subject variability than others. Average repeatability data (within subject SD) for each test were calculated, and included deep breathing sitting (max-min) RR (46 ms), Valsalva ratio (0.17), and lying to standing RR ratio (0.11). These compare with between subject SDs of 65 ms, 0.38, and 0.13 respectively, at mean values of 305 ms, 1.92, and 1.15 respectively. The data highlighted one subject with the poorest repeatability, whose electrocardiogram turned out on closer inspection to be under atrial rather than sinus control at times. Poor repeatability in the other subjects was related to variability in the respiratory pattern, and in the deep breathing test, repeat variability was significantly correlated (r = 0.79) with variability in the respiratory amplitude (p < 0.05). CONCLUSIONS: Repeatability data should be available to each laboratory carrying out autonomic function tests. The data provided in this study could be used as a baseline. Poor repeatability highlights the need to re-examine the test procedures, or the test data from specific subjects. Variability of respiratory pattern is associated with poor repeatability, and so careful instructions on respiration should be given to each subject before the tests.
Adult↗
Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis.
Hepatic insulin extraction is difficult to measure in humans; as a result, the interrelationship between defective insulin secretion and insulin insensitivity in the pathogenesis of glucose intolerance in cirrhosis remains unclear. To reassess this we used recombinant human C-peptide to measure C-peptide clearance in cirrhotic patients and controls and thus derive C-peptide and insulin secretion rates after a 75-gm oral glucose load and during a 10 mmol/L hyperglycemic clamp. Cirrhotic patients were confirmed as insulin-insensitive during a euglycemic clamp (glucose requirement: 4.1 +/- 0.1 mg/kg/min vs. 8.1 +/- 0.5 mg/kg/min; p less than 0.001), which also demonstrated a low insulin metabolic clearance rate (p less than 0.001). Although intolerant after oral glucose, the cirrhotic patients had glucose requirements identical to those of controls during the hyperglycemic clamp (cirrhotic patients: 6.1 +/- 1.0 mg/kg/min; controls: 6.3 +/- 0.7 mg/kg/min), suggesting normal intravenous glucose tolerance. C-peptide MCR was identical in cirrhotic patients (2.93 +/- 0.16 ml/min/kg) and controls (2.96 +/- 0.24 ml/min/kg). Insulin secretion was higher in cirrhotic patients, both fasting (2.13 +/- 0.26 U/hr vs. 1.09 +/- 0.10 U/hr; p less than 0.001) and from min 30 to 90 of the hyperglycemic clamp (5.22 +/- 0.70 U/hr vs. 2.85 +/- 0.22 U/hr; p less than 0.001). However, with oral glucose the rise in serum C-peptide concentration was relatively delayed, and the insulin secretion index (secretion/area under 3-hr glucose curve) was not elevated. Hepatic insulin extraction was reduced both in fasting and during the hyperglycemic clamp (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
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↗
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↗
Management of newly diagnosed non-insulin-dependent (type 2) diabetes mellitus: a retrospective audit.
A retrospective survey of the case records of 130 patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) was performed to assess the effect of 1 year of clinical attendance on blood glucose control, body weight, lipid profile and blood pressure. The mean age of these patients was 63 +/- (SE) 0.1 years and 45% were 65 years or older. Body mass index (BMI) was 28.3 +/- 0.49 kg m-2 and 72% were overweight or obese. Sixty-seven percent of the patients were hypertensive (WHO criteria). Serum cholesterol was 6.0 +/- 0.2 mmol/l, HDL cholesterol 1.0 +/- 0.0 mmol/l and triglycerides 3.14 +/- 0.29 mmol/l (non-fasting). Seventy-two percent of the patients were managed on diet alone and 23% by diet plus sulphonylurea. The remaining 5% were treated by metformin or a combination of metformin plus sulphonylurea. After one year, glycated haemoglobin (HbA1) decreased from 10.7 +/- 0.3% to 8.2 +/- 0.2% (P less than 0.01; normal less than 7.5%). The sulphonylurea groups showed similar decreases in HbA1. Overall there was a small but significant fall in BMI (-0.5 +/- 0.2 kg m-2; P less than 0.05). However, the diet treated patients showed a significant decrease in BMI (-0.8 +/- 0.3 kg m-2; P less than 0.01) whilst BMI increased in the sulphonylurea treated group (+0.7 +/- 0.2 kg m-2; P less than 0.01). Serum lipid concentrations remained unchanged in both groups. The proportion of patients with hypertension remained the same. Hence after one year of clinical attendance, HbA1 improved but there was minimal change in the associated cardiovascular risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Does flexibility at mealtimes disturb blood glucose control on a multiple insulin injection regimen?
Randomized crossover studies of a half-sized lunch with reduced insulin dose in 21 patients, and a delayed (by 2 h) evening meal in 22 patients, compared with normal meals, were performed in Type 1 diabetic patients. The aim was to examine whether the size and timing of meals can be varied in patients on multiple injection regimens without disturbance of blood glucose control. All patients had previously had their control optimized on multiple injection therapy using a pen-injector. The studies were carried out at home on 6 days (3 changed meals, 3 control) over 2 months, and as 8- and 7-h metabolic profiles (1 study day, 1 control) in an investigation unit. A halved calorie lunch with half the usual insulin dose resulted in equivalent blood glucose control on the study day (area under curve: changed meal 40.0 +/- 3.4 vs control meal 40.3 +/- 3.5 mmol l-1 h for the 5-h period after the meal). Ketone body levels were also unchanged. The late evening meal shifted the post-prandial blood glucose concentration accordingly, but the excursion was not different in extent from the control day (24.8 +/- 1.9 vs 21.0 +/- 1.7 mmol l-1 h). A small excursion of 3-hydroxybutyrate levels before the delayed meal (to 187 +/- 48 mumol l-1) was quickly corrected on eating. Hypoglycaemia was not different in frequency on the changed meal days. Thus no problems of clinical significance were observed when some flexibility in meal size and timing was allowed.
Adult↗
Time delay compensation for closed-loop insulin delivery systems: a simulation study.
Closed loop insulin therapy certainly represents the best possible approach to insulin replacement. However, present limitations preclude wider application of the so-called artificial pancreas. Therefore, a thorough understanding of these limitations is needed to design better systems for future long-term use. The present simulation study was design: to obtain better information on the impact of the measurement delay of currently available closed-loop devices both during closed-loop insulin delivery and blood glucose clamp studies, and to design and test a time delay compensator based on the method originally described by O.J. Smith. Simulations were performed on a Compaq Deskpro 486/25 personal computer under MS-DOS operating system using Simnon rel. 3.00 software. There was a direct relationship between measurement delay and amount of insulin delivered, i.e., the longer the delay the higher the insulin dose needed to control a rise in blood glucose; the closed-loop response in presence of a time delay was qualitatively impaired both during insulin delivery and blood glucose clamp studies; time delay compensation was effective in reducing the insulin dose and improving controller stability during the early phase of clamp studies. However, the robustness of a Smith's predictor-based controller should be carefully evaluated before implementation in closed-loop systems can be considered.
Computer Simulation↗
Total-body potassium in insulin-dependent diabetes mellitus.
1. Total-body potassium and fat-free mass have been measured in 31 insulin-dependent diabetic patients and 31 age- and sex-matched normal volunteers. 2. Body mass index was significantly higher in the insulin-dependent diabetic patients (24.7 +/- 0.5 vs 23.3 +/- 0.4 kg/m2; P = 0.05). 3. Total-body potassium, uncorrected and corrected for weight and for fat-free mass, was not significantly different in the two groups (3281 +/- 141 mmol, 47.3 +/- 1.3 mmol/kg body weight, 60.9 +/- 1.0 mmol/kg fat-free mass, and 3315 +/- 143 mmol, 48.6 +/- 1.0 mmol/kg body weight, 60.4 +/- 0.8 mmol/kg fat-free mass, respectively, in diabetic patients and non-diabetic subjects). There was no relationship between blood glucose control, as assessed by glycated haemoglobin concentrations, and total-body potassium. 4. These results suggest, by contrast with previous reports, that in insulin-dependent diabetic patients, showing varying degrees of glycaemic control (glycated haemoglobin range 6.1-15.3%, mean 9.0%) that: (a) there is no significant abnormality of body potassium homoeostasis, and (b) there is no relation between total-body potassium and glycaemic control.
Adolescent↗
Different absorption of isophane (NPH) insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique.
The absorption of isophane (NPH) insulin from subcutaneous and intramuscular injection sites was measured in seven healthy volunteers using the euglycaemic clamp technique. Human Insulatard (Nordisk, Gentofte, Denmark) was administered in a dose of 0.25 U kg-body-weight-1 into the anterior compartment of the thigh. In random order injections were given either subcutaneously, via 12 mm needle at 45 degrees to the skin into a skinfold, or intramuscularly by 25 mm needle perpendicularly to the skin. Insulin concentrations rose more rapidly after intramuscular injection than after subcutaneous injection, being significantly higher as early as 60 min after injection (19.7 +/- 1.6 (+/- SE) vs 8.7 +/- 1.4 mU l-1; p less than 0.001). Thereafter insulin concentrations remained significantly higher for the remaining 360 min of study, reflected by a significantly greater area under the insulin concentration curve for the 420 min study (IM 8630 +/- 1256 vs SC 4908 +/- 465 mU l-1 min, p less than 0.05). A significantly greater quantity of infused glucose was required to maintain euglycaemia after intramuscular injection than after subcutaneous injection (923 +/- 256 vs 216 +/- 71 mg kg-1 min, p less than 0.05). These results demonstrate a striking difference in the pharmacokinetics of an isophane (NPH) insulin when injected into subcutaneous fat and muscle.
Adult↗
Morphology of palpably abnormal injection sites and effects on absorption of isophane(NPH) insulin.
The absorption of isophane(NPH) insulin (Human Insulatard) from palpably abnormal thigh insulin injection sites was determined in 10 C-peptide negative diabetic patients. Absorption was compared with a control day study when the insulin was injected into normal thigh. Standard meals were given 30 and 240 min after the injection. Within 2 weeks the tissue morphology and adipose tissue depths at both injection sites were assessed by ultrasound scanning. Absorption of isophane(NPH) insulin was markedly defective from the abnormal compared with the normal injection sites (area under the free insulin curve to 10 h 115 +/- 15 vs 188 +/- 21 mU l-1 h; p less than 0.01). The area under the blood glucose curve from 270 min to the end of the study at 600 min was significantly greater after injection into the palpably abnormal injection site compared with normal thigh (80.4 +/- 5.2 vs 61.2 +/- 7.0 mmol l-1 h; p less than 0.05) representing a 22% improvement in blood glucose control on the normal injection site afternoon. The depth of abnormal injection site tissue was significantly greater than the depth of adipose tissue at the control site (17 +/- 6 vs 5 +/- 4 mm; p less than 0.001) and considerable disruption of the normal anatomy observed. These results demonstrate defective absorption of isophane(NPH) insulin from palpably abnormal injection sites and describe the morphology of the abnormal tissue.
Absorption↗