Role of Itolizumab in the Treatment of COVID-19 Patients, Admitted to ICU at a Tertiary Care Hospital.

BACKGROUND: Clinical studies have correlated severe deterioration of COVID-19 patients due to excessive and uncontrolled production of cytokines. There is a pressing need to explore therapies, which could prevent the cytokine storm rather than terminating it. AIMS AND OBJECTIVES: The aim of the study is to evaluate the effect of itolizumab on clinical outcomes of patients with moderate-severe COVID-19 disease admitted to ICU. The primary aim of the current study is to find out any mortality benefit in 14 days. The secondary aim is to assess the morbidity outcomes in terms of reduction in inflammatory markers and also the duration of hospital stays to assess the prognostication. MATERIALS AND METHODS: It is a retrospective case-control study in which laboratory-confirmed COVID-19 patients admitted to ICU were taken. A total of 62 patients were recruited, 31 patients received itolizumab (cases/treatment group) and 31 patients didn't receive itolizumab (designated as controls). RESULTS: Among the total patients recruited, 68% of the study population was male and 32% were female. A total of 12 patients expired among cases and 13 expired among controls. Overall mortality in both groups was noted to be almost similar. The control group showed mortality at lower computed tomography (CT) scores compared to the cases. There is a significant reduction in inflammatory markers, like interleukins-6 (IL-6) and D-dimer in cases compared to the control group. CONCLUSION: In conclusion, treating patients with cytokine storms before they require intubation/mechanical ventilation is crucial to preventing deaths. Itolizumab has shown no clinical benefit in critically ill COVID-19 patients, however, timely initiation of itolizumab therapy may serve as a key therapeutic option in preventing the mortality and morbidity outcomes in moderate-severe COVID-19 patients.

The impact of COVID-19 on rheumatology patients in a large UK centre using an innovative data collection technique: prevalence and effect of social shielding.

OBJECTIVES: We sought to gain insight into the prevalence of COVID-19 and the impact stringent social distancing (shielding) has had on a large cohort of rheumatology (RD) follow-up patients from a single large UK centre. METHODS: We linked COVID-19-related deaths, screening and infection rates to our RD population (1.2.20-1.5.20) and audited active rheumatology follow-up patients through survey data communicated via a linked mobile phone SMS message. We assessed epidemiology, effect of stringent social distancing (shielding) and quality of life (HRQoL) by Short Form 12 (SF12). RESULTS: There were 10,387 active follow-up patients, 7911 had linked mobile numbers. 12/10,387 RD patients died from COVID-19 (0.12%); local population 4131/7,415,149 (0.12%). For patients with mobile phones, 1693/7911 (21%) responded and of these, 1605 completed the SF12. Inflammatory arthritis predominated 1174/1693 (69%); 792/1693 (47%) were shielding. Advice on shielding/distancing was followed by 1372/1693(81%). 61/1693 (4%) reported COVID-19 (24/61 shielding); medication distribution was similar in COVID and non-COVID patients. Mental SF12 (MCS) but not physical (PCS) component scores were lower in COVID (60) vs. non-COVID (1545), mean differences: MCS, - 3.3; 95% CI - 5.2 to - 1.4, P < 0.001; PCS, - 0.4; 95% CI, - 2.1 to 1.3). In 1545 COVID-negative patients, those shielding had lower MCS (- 2.1; 95% CI - 2.8 to - 1.4) and PCS (- 3.1, 95% CI - 3.7 to - 2.5), both P < 0.001. CONCLUSIONS: Our full RD cohort had no excess of COVID deaths compared to the general local population. Our survey data suggest that shielding adversely affects both mental and physical health in RD. These data broaden our understanding of shielding, indicating need for further study.

Synergistic protective effect of picrorhiza with honey in acetaminophen induced hepatic injury.

Rhizome of picrorhiza along with honey prevents hepatic damage and cure the acetaminophen (paracetamol) induced hepatotoxicity by modulating the activity of hepatic enzymes. Here, we studied the in vivo effects of Picrorhiza kurroa and honey on acetaminophen induced hepatotoxicity Balb/c mice model. Hepatic histopathological observations of acetaminophen fed (day-6) group showed more congestion, hemorrhage, necrosis, distorted hepatic architecture and nuclear inclusion. Such damages were recompensed to normal by picrorhiza or honey alone or both in combinations. We observed increased activity of SGPT and SGOT in injured liver tissues, and that too was compensated to normal with picrorhiza or honey alone or both in combinations. We observed 1.27 and 1.23-fold enhanced activity of SGPT in serum and liver lysate, respectively while SGOT showed 1.66 and 1.11 fold enhanced activity. These two enzymes are signature enzymes of liver damage. Thus, our results support that honey may be used with drug picrorhiza due to its synergistic role to enhance hepatoprotective and hepatoregenerative ability along with allopathic drugs to mitigate the hepatotoxic effects.

Provision of structured diabetes information encourages activation amongst people with diabetes as measured by diabetes care process attainment: the WICKED Project.

BACKGROUND: People with diabetes have better outcomes if they actively participate in their care. Patient-focused interventions can be effective in activating patients. Yet there is no known trial to evaluate the impact of the provision of individualized diabetes-specific information on patient activation and diabetes care outcomes. METHODS: In a randomized controlled trial, all people (n = 14 559) with diabetes within the local health economy were recruited and cluster randomized into two groups with the active group mailed a structured personalized report containing information on all nine of their diabetes care processes, whereas the control group received standard care. Differences in their Failed Process Score (FPS) were compared at three months. RESULTS: At three months, the FPS score (1.25 ± 1.87 vs. 1.35 ± 1.97, P < 0.01) and the change in FPS score (0.48 ± 1.55 vs. 0.42 ± 1.49, P < 0.02) were significantly better in those mailed a structured personalized report. A dichotomized FPS score [good attainment (GA) vs. poorer attainment], was significantly better in those mailed (χ2 = 10.0, P < 0.05) and using a binary logistic regression analysis adjusting for all demographic factors and the baseline FPS, the relative effect of mailing compared with non-mailing on three-month GA category was OR 1.14 (95% CI 1.04-1.25, P < 0.01). CONCLUSIONS: Provision of structured and individualized information to people with diabetes can positively influence the level of patient activation, promote better engagement and open the potential to improve other crucial diabetes outcomes.

LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.

The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase. Additionally, variable degrees of resistance to insulin action, together with a hyperlipidaemic state, may occur and simulate the metabolic features commonly associated with predisposition to atherosclerotic disease. The PLD locus has been mapped to chromosome 1q with no evidence of genetic heterogeneity. We, and others, have refined the location to a 5.3-cM interval between markers D1S305 and D1S1600 (refs 5, 6). Through a positional cloning approach we have identified five different missense mutations in LMNA among ten kindreds and three individuals with PLD. The protein product of LMNA is lamin A/C, which is a component of the nuclear envelope. Heterozygous mutations in LMNA have recently been identified in kindreds with the variant form of muscular dystrophy (MD) known as autosomal dominant Emery-Dreifuss MD (EDMD-AD; ref. 7) and dilated cardiomyopathy and conduction-system disease (CMD1A). As LMNA is ubiquitously expressed, the finding of site-specific amino acid substitutions in PLD, EDMD-AD and CMD1A reveals distinct functional domains of the lamin A/C protein required for the maintenance and integrity of different cell types.

Relationship between erythrocyte GLUT1 function and membrane glycation in type 2 diabetes.

This paper investigates the effect of glycation on glucose transport in erythrocytes. Glucose transporter function, numbers and erythrocyte phosphorylation rates are simultaneously studied using 30 Caucasian patients with diabetes and 30 Caucasian control volunteers (mean +/- SD where P < or = 0.05; age 48 +/- 8 vs. 45 +/- 8 years [ns]; body mass index [BMI] 31 +/- 7 vs. 27 +/- 5 [P=0.035]; blood glucose 12 +/- 7 vs. 5 +/- 0.6 mmol/L [P=0.001]; HbA1c 8 +/- 2 vs. 5 +/- 0.3% [P=0.0001]; fructosamine 336 +/- 64 vs. 237 +/- 16 micromol/L [P=0.0001]; disease duration 13 +/- 11 years, respectively). Significant differences were found for glucose transporter function, with 3-O-methylglucose uptake rates (108 +/- 49 vs. 146 +/- 55 micromol/L/sec/10(12) cells [P=0.010]); D-glucose influx (64 +/- 30 vs. 117 +/- 45 micromol/L/sec/10(12) cells [P=0.0001]); and D-glucose net transport (31 +/- 22 vs. 74 +/- 55 micromol/L/sec/ 10(12) cells [P = 0.0001]). No differences were found for phosphorylation rates using 2-deoxyglucose (33 +/- 17 vs. 38 +/- 12 micromol/L/sec/10(12) cells [P=0.194]). The number of functional transporters using cytochalasin B studies measured via B(max), was not found to be significantly different between the groups (195 +/- 139 vs. 264 +/- 174 [P=0.206]). However, K(d) was lower for those with diabetes, suggesting higher binding affinity (12 +/- 11 vs. 32 +/- 25 nmol/L [P=0.006]). A negative correlation between HbAlc and D-glucose influx involving both groups was found (r=-0.670, P=0.0001). Glucose transport is shown to be decreased in people who have diabetes compared to normoglycaemic volunteers, whereas the number of glucose transporters is apparently unchanged; however, affinity for binding is increased.

Thyrotoxicosis factitia masquerading as recurrent Graves' disease: endogenous antibody immunoassay interference, a pitfall for the unwary.

Antibody interference in immunoassays is an underestimated problem, which has the potential to cause patient harm and waste health-care resources. We report a case where thyroglobulin antibodies generated a false-positive thyroglobulin result delaying the diagnosis of thyrotoxicosis factitia masquerading as recurrent Graves' disease. A high index of clinical suspicion and good laboratory-clinician communication underpins effective clinical and laboratory strategies to detect potentially erroneous laboratory results due to endogenous antibody interference in immunoassays.

Efficacy, acceptability and side effects of the levonorgestrel intrauterine system for menorrhagia.

OBJECTIVE: To evaluate the efficacy, acceptability, and possible side effects of a levonorgestrel-releasing intrauterine system for menorrhagia. METHODS: Sixty-three women with menorrhagia but without uterine enlargement, endometrial hyperplasia with atypia, or endometrial carcinoma were enrolled in this prospective, open, nonrandomized clinical trial. An intrauterine system releasing 20 microg/day of levonorgestrel (LNG-IUS; Mirena, Shering, Finland) was inserted in the postmenstrual phase. Menstrual pattern, number of bleeding days, and subjective and objective estimation of menstrual blood loss using a pictorial blood loss assessment chart (PBAC) were recorded before insertion and at specific intervals for 4 years. Hemoglobin levels and endometrial thickness were evaluated at baseline and at 12 months. Treatment continuation and hysterectomy rates were noted as well as side effects. RESULTS: The device was expelled spontaneously in 6 patients (9.52%) and removed prematurely in 9 patients (14.3%); 3 patients (4.8%) were lost to follow-up; and 45 patients (71.4%) continued with the LNG-IUS. Menorrhagia was cured in 35 (77.7%) of these 45 patients at 3 months and in all patients at 36 months. There was a significant decrease in the mean number of bleeding days (P=0.01) and PBAC score (P=0.00) at 1 month, and the decrease continued with treatment duration. The subjective blood loss reduction was considerable as well, and at 12 months the mean+/-SD rise in hemoglobin concentration was 1.06+/-1.7 g/dL (P=0.000). Endometrial thickness was decreased by 3.4+/-3.53 mm (P=0.0001) at 12 months. The most common side effect was intermenstrual spotting during the first 6 months, and 18 patients (28.57%) developed amenorrhea. CONCLUSION: Using the LNG-IUS is an effective and well-accepted option overall for the medical management of menorrhagia.

Multiple aspects of insulin resistance. Comparison of glucose and intermediary metabolite response to incremental insulin infusion in IDDM subjects of short and long duration.

Glucose and intermediary metabolite responses during incremental insulin infusion (basal, 0.005, 0.01, and 0.05 U X kg-1 X h-1) were examined in IDDM subjects with duration of diabetes of greater than 5 yr (group D5: n = 8, duration 13.5 +/- 3.9 yr, mean +/- SD) and less than 1 yr (group D1: n = 8, duration 0.3 +/- 0.1 yr) from diagnosis. Group D5 had significantly elevated basal plasma free-insulin levels (D5 27.4 +/- 9.6, D1 15.5 +/- 9.4 mU/L; P less than .05). Nonetheless, basal blood glucose (D5 13.8 +/- 4.8, D1 7.1 +/- 1.5 mM; P less than .01), plasma nonesterified fatty acid (NEFA) (D5 1.26 +/- 0.12, D1 0.89 +/- 0.10 mM; P less than .01), blood glycerol (D5 0.12 +/- 0.05, D1 0.07 +/- 0.02 mM; P less than .05), and blood ketones (D5 1.25 +/- 0.91, D1 0.26 +/- 0.20 mM; P less than .01) were higher in group D5. During insulin infusion, group D5 had significantly elevated plasma free-insulin (P less than .05) and blood glucose (P less than .01) levels. Isotopically determined glucose turnover showed metabolic clearance rates were significantly diminished in group D5 during all insulin infusions, indicating a marked impairment of peripheral glucose metabolism. In individual subjects the relationship of blood glucose, plasma NEFA, and blood total ketones (log scale) with the simultaneously occurring plasma insulin level (log scale) was linear for each metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension-based clinical risk strategies for detecting microalbuminuria in diabetes.

BACKGROUND: Microalbuminuria screening to identify patients at risk of diabetic nephropathy is widely accepted. AIM: To investigate whether blood-pressure-based strategies can identify such patients without the need for microalbuminuria testing. METHODS: Spot urine for albumin/creatinine ratios was performed in all patients over an 18-month period. The performance of four combinations of clinical models, based on existing triggers for anti-hypertensive intervention (prior use and/or existing systolic BP exceeding 140 or 160 mmHg and/or dipstick proteinuria exceeding 1+ or 2+) was evaluated at microalbuminuria thresholds of 3.5 and 10 mg/mmol. The models were ranked 1 to 4, based on their escalating relative strengths in predicting need for intervention. RESULTS: Of 3748 patients, 1257 (34%) or 739 (20%) exceeded microalbuminuria thresholds of 3.5 or 10 mg/mmol. All four models predicted microalbuminuria risk (areas under ROC curves 0.60-0.77, all p < 0.001). The models (1-4) identified 2220, 2465, 2803 or 2937 for intervention, respectively, irrespective of microalbuminuria status, and missed 368, 232, 194 or 126 at 3.5 mg/mmol and 164, 87, 81 or 45 at 10 mg/mmol. DISCUSSION: Clinical models using routinely measured parameters reduced the target population for microalbuminuria screening by 60-80%, missing 3-10% of patients with albumin/creatinine ratios exceeding 3.5 mg/mmol or 1-4% of those exceeding 10 mg/mmol.

High variability of glycated hemoglobin concentrations in patients with IDDM followed over 9 years. What is the best index of long-term glycemic control?

OBJECTIVE: To determine variability of long-term glycemic control in patients with IDDM. RESEARCH DESIGN AND METHODS: A retrospective analysis of HbA1 among 122 IDDM patients followed over 9 years. RESULTS: Annual group mean HbA1 ranged from 8.4 to 9.3% with large standard deviations (1.7-2.0%), indicating marked variability among individuals. Fluctuations of more than +/- 1% HbA1 occurred in 50% of the patients year to year, and over 9 years the minimum-maximum range was > 3 and > 5% HbA1 in 55 and 11% of patients, respectively. In any one year, 22-43% of patients had HbA1 < 8%, but over 9 years only 3.3% were consistently < 8%. Groups divided according to baseline HbA1 of < 8, 8-10, and > 10% were significantly separated over 9 years by frequency distribution analysis of individual mean HbA1 but were indistinguishable when analyzed by individual HbA1 interquartile range (measure of variability). CONCLUSIONS: High variability of long-term glycemic control is a marked feature of IDDM, the extent of which may be relevant to microvascular risk.

Hypertensive cerebrovascular disease and normal pressure hydrocephalus.

A hypertensive patient with clinical and laboratory features of normal pressure hydrocephalus (NPH) but with evidence of bilateral multiple cerebral infarcts on computed tomography (CT) did not benefit from shunting. In six reported cases of hypertensive cerebrovascular disease with NPH, the result of shunting was not predictable and was generally disappointing. Laboratory criteria to predict which cases of NPH will benefit from shunting remain controversial. The chances of improvement after shunting are slight when there is CT evidence of bilateral multiple cerebral infarcts, even though other clinical and laboratory data might suggest NPH.

Prevalence of hypovitaminosis D in Indo-Asian patients attending a rheumatology clinic.

This study was performed to determine the prevalence of hypovitaminosis D (HD) and hypovitaminosis D associated with secondary hyperparathyroidism (HD-SHPT) among Indo-Asians attending rheumatology clinics in Wolverhampton. A cross-sectional survey of 98 clinic attenders and 36 normal controls subjects was undertaken. The groups were matched for age, gender, and body mass index. There was a high prevalence of vegetarianism, and milk consumption was low in both groups. Clinical scores for musculoskeletal pain, gait, and muscle strength were all significantly worse in clinic attenders (p < 0.001). Comparing clinic attenders with controls, 25-OH-vitamin D levels were 6.6 +/- 3.9 vs. 8.2 +/- 4.8 microg/L (p < 0.01) and the prevalence of HD (<8 microg/L) was 78% vs. 58% (p < 0.05), but neither parathyroid hormone levels (53 +/- 60 vs. 50 +/- 18 ng/L, n.s.) nor HD-SHPT prevalence (22% vs. 33%, n.s.) were significantly different. Routine biochemical tests were not discriminant, but none of the controls and 10 of 98 (10%) clinic attenders had elevated alkaline phosphatase levels: 6 with HD and 3 with HD-SHPT. Vitamin D deficiency has an extremely high prevalence among Indo-Asians in the U.K., particularly in those attending rheumatology clinics. Detection of HD and HD-SHPT is only possible using measurements of 25-OH-vitamin D and PTH.

Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion.

Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 +/- 11.5 v 22.1 +/- 2.2 kg.m-2; mean +/- SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 +/- 3.8 v 2.4 +/- 3.0 mU.L-1, P less than .001) and remained elevated throughout infusion (F = 492, P less than .001), as did C-peptide (F = 22.7, P less than .001). Metabolic clearance rate for insulin (MCRI) at the highest infusion rate was similar (1,048 +/- 425 v 1,018 +/- 357 mL.m-2.min-1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 +/- 108 v 444 +/- 68 mumol.m-2.min-1, P less than .01), as was the basal metabolic clearance rate for glucose (MCRG, 77 +/- 26 v 108 +/- 31 mL.m-2.min-1, P less than .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 +/- 0.5 v 1.9 +/- 0.5 mmol.L-1, P less than .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL.m-2.min-1/mU.L-1, P less than .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were elevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Following weight loss in massively obese patients correction of the insulin resistance of fat metabolism is delayed relative to the improvement in carbohydrate metabolism.

Intermediary metabolite and serum insulin concentrations have been measured during incremental intravenous low-dose insulin infusion in massively obese patients before, and 3 months and 12 months after gastroplasty. Fasting blood glucose was similar on the three occasions, but fasting serum insulin was significantly higher preoperatively and showed a progressive fall with weight loss. Significant negative linear correlations were found between serum insulin and blood glucose, plasma nonesterified fatty acids, blood glycerol and blood total ketone bodies concentrations. The insulin-glucose dose-response curve showed a significant left shift at 3 months with a further significant improvement at 12 months. No significant change in the responses for nonesterified fatty acids, glycerol, and ketone bodies was observed at 3 months, but all three showed a significant left shift at 12 months. Massively obese patients are resistant to the action of insulin on carbohydrate and fat metabolism. Weight loss following gastroplasty results in an improvement in sensitivity to insulin, which is evident earlier in carbohydrate metabolism than in fat metabolism.

Hypertension in diabetes: is there a place for age-adjusted centile cut-offs in those aged <50 years?

BACKGROUND: Conventional cut-offs for hypertension are arbitrary, and vascular complications can occur below these values, particularly in diabetes. AIM: To evaluate systolic blood pressure (SBP) distribution in diabetes and control populations, comparing hypertension prevalence using either conventional cut-offs (140 and 160 mmHg) or age-adjusted centile (75(th) and 90(th)) cut-offs derived from the control population. METHODS: We compared 2521 individuals with diabetes to 5809 controls, after excluding those on anti-hypertensives and with established vascular disease in both groups. RESULTS: Diabetic individuals were older (mean +/- SD 56 +/- 16 vs. 43 +/- 16years, diabetes vs. controls), and had higher BMI (29 +/- 5 vs. 24 +/- 4 kg /cm(2)) and SBP (145 +/- 23 vs. 131 +/- 18 mmHg, all p < 0.001). These factors were adjusted for in subsequent analysis. SBP rose with age and was also significantly higher in the diabetes group. In diabetes, conventional cut-offs indicated less hypertension in those aged < 50 years, compared to age-adjusted centile cut-offs. In age bands 18-29, 30-39, 40-49, 50-59, 60-69 and >70 years of the diabetes group, 24%, 33%, 43%, 62%, 70% and 74%, respectively exceeded 140 mmHg, compared to 35%, 44%, 43%, 45%, 40% and 27% exceeding the control-derived 75(th) centile value. DISCUSSION: The use of control-derived age-adjusted cut-offs may provide an alternative approach to define hypertension in diabetes that may be of particular relevance to younger patients, although this would require validation against outcomes.

The effects of verapamil, diltiazem, nifedipine and propranolol on metabolic control in hypertensives with non-insulin dependent diabetes mellitus.

The effects of one month's treatment with each of nifedipine, verapamil, diltiazem, propranolol and placebo, given in random order, on fasting plasma glucose, haemoglobin Alc, serum fructosamine, immunoreactive insulin, cholesterol, and triglyceride were studied in a group of 19 patients with hypertension and non-insulin dependent diabetes mellitus. The metabolic effects of the active drugs were generally small but fasting plasma glucose was increased by propranolol from 9.3 +/- 3.0 to 10.4 +/- 3.4 mmol/l (P less than 0.01) (mean +/- SD) and to 10.1 +/- 3.2 mmol/l (P less than 0.05) by nifedipine. Serum fructosamine was increased from 2.75 +/- 0.53 to 2.89 +/- 0.62 mmol/l (P less than 0.05) by diltiazem and to 2.91 +/- 0.65 (P less than 0.05) by propranolol. Verapamil increased fasting serum immunoreactive insulin: diltiazem and propranolol tended to reduce it. Propranolol but not the other drugs significantly increased serum triglyceride. Calcium antagonists may be preferable to beta adrenoceptor blockers for the treatment of hypertensive diabetics. Of the three calcium antagonists we studied, verapamil may have advantages over nifedipine and diltiazem.

Insulin resistance in the regulation of lipolysis and ketone body metabolism in non-insulin dependent diabetes is apparent at very low insulin concentrations.

The insulin sensitivity of intermediary metabolism was studied in 8 non-obese men with well-controlled diet-treated non-insulin dependent diabetes (NIDDM) using a low dose incremental insulin infusion (basal, 0.005 and 0.01 U/kg h-1). Results were compared to 8 healthy male control subjects matched (NIDDM vs. controls, mean +/- S.E.M.) for age (56 +/- 3 vs. 54 +/- 3 years, NS) and body mass index (24.6 +/- 0.7 vs. 25.3 +/- 0.5 kg/m2, NS). Basal fasting concentrations of insulin (4.7 +/- 0.8 vs. 3.2 +/- 0.8 mU/l, NS), glucose, total ketone bodies (TKB), and non-esterified fatty acids (NEFA) were not significantly different between the groups but glycerol concentrations were significantly elevated in NIDDM patients (0.072 +/- 0.007 vs. 0.049 +/- 0.003 mmol/l, P < 0.05). During incremental insulin infusion, plasma insulin concentrations rose to 12.8 +/- 1.5 vs. 10.0 +/- 1.0 mU/l in NIDDM patients vs. control and metabolite concentrations fell significantly (P < 0.001). Significant linear dose-response relationships were found between plasma insulin (log) and glucose, TKB (log), NEFA, and glycerol concentrations by analysis of variance applied to regression (all P < 0.001). For glucose and TKB (log), the group regression lines were parallel but were significantly right-shifted in the NIDDM group (P < 0.001). In contrast, the relationships of insulin (log) and both glycerol and NEFA concentrations converged over the observed range of insulin concentrations. Significant displacement of glycerol and NEFA dose-response relationships were found in NIDDM patients at an insulin concentration of 5 mU/l (P < 0.001) but not at 12.5 mU/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Type 1 diabetes mellitus in a routine diabetes clinic: the association of psycho-social factors, diabetes knowledge and glycaemic control to insulin regime.

In controlled trials intensified diabetes therapy including multiple insulin injection regimes has been shown to improve glycaemic and microvascular disease outcomes in insulin dependent diabetes but this is not clear in routine outpatient practice. We undertook a pragmatic cross sectional study of 200 patients with Type 1 diabetes aged 18-50 years. There were 108 on two insulin injections/day (conventional) and 92 on four injections/day (multiple) with no significant difference for age, sex, social class, body mass index, diabetes duration, hypoglycaemia rate or complications prevalence. The relationship of insulin injection regime used with diabetes knowledge, psychological factors and glycaemic control outcomes was evaluated. Percent glycated HbA1c concentrations (normal range < 5.5%) were worse in the multiple injection group (7.5 +/- 1.7 vs. 6.8 +/- 1.4%, P < 0.001) (mean +/- SD). Their scores for diabetes knowledge (72.5 +/- 8.2 vs. 69.0 +/- 9.8, P < 0.01) were better but treatment satisfaction (29.9 +/- 5.1 vs. 28.5 +/- 6.1, ns) and well-being (49.1 +/- 10.7 vs. 46.5 +/- 12.7, ns) scores were not. Parameters of perceived locus of control were (multiple v conventional): personal (self), 24.5 +/- 5.0 vs. 22.3 +/- 5.9, P < 0.05; medical (doctor), 11.8 +/- 5.1 vs. 10.8 +/- 5.8, ns; situational (chance), 7.9 +/- 5.1 vs. 8.9 +/- 5.9, ns. In multiple regression of HbA1c versus multiple variables only insulin regime (P < 0.001) was significant. We conclude that in routine clinical practice the use of intensive insulin regimes are associated with worse glycaemic control despite patients being marginally more knowledgeable and self directed.