Global perspectives on the provision of diabetic retinopathy screening and treatment: Survey of health care professionals in 41 countries.

AIM: To assess the level of awareness and provision of screening and treatment for Diabetic Eye Disease (DED) comprising Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME) among health care professionals. METHODS: The study was conducted in two phases. The first phase consisted of a qualitative study, based on semi-structured face-to-face and telephone interviews in 8 countries. The second phase used a quantitative approach utilising online surveys in 41 countries. The survey for health care professionals comprised of 43 questions covering provider information, practice characteristics, management of adults with diabetes and specific information from ophthalmologists on screening and treatments for DR. RESULTS: There were 2329 health care professionals who participated in the online survey. More than one third of diabetes specialists surveyed reported that they did not discuss eye care with their diabetes patients. Nearly two-thirds of all health care professionals surveyed reported that they had written information about diabetes for patients available in their practice. Only one in five (22%, n = 58) primary care providers reported they had material that contained sufficient information on eye complications, and 37% (n = 252) of ophthalmologists reported that they had sufficient information on eye complications. Sixty-five percent (n = 378) of ophthalmologists reported that most of their patients presented when visual problems had already occurred. Six percent (n = 36) stated that most of their patients presented when it was already too late for effective treatment. The most substantial barriers to eye health mentioned by health care professionals responding to the survey were: a patients' lack of knowledge and/or awareness about eye complications (43%), followed by lack of importance given to eye examinations by patients (33%), and the high cost of care (32%). Ophthalmologists also reported late screening (66%), and lack of patient education materials (55%) as obstacles for improving eye health outcomes. CONCLUSION: Health care professionals need to be appropriately supported and trained so they can provide adults with diabetes with information about the risks of DR, support them in reducing their risk, and advocate for the provision of affordable DR screening and treatment as required.

Sustaining diabetes prevention and care interventions: A multiple case study of translational research projects.

BACKGROUND: This study identifies the barriers and enablers for sustainability of interventions in primary and secondary prevention of diabetes. In the context of translational research, sustainability is defined as the continued use of program components and activities for the continued achievement of desirable program and population outcomes. METHODS: In this study, eleven translational research projects, supported by the BRIDGES program of the International Diabetes Federation, were investigated. By theoretically-informed semi-structured interviews and analyses of project reports, qualitative data was collected on the sustainability outcomes and the barriers and enablers. RESULTS: The sustainability outcomes can be grouped in three main areas: (1) sustainability at the intervention site(s); (2) diffusion to the wider community; and (3) replication of the intervention at other site(s). Each of the outcomes has their own set of enablers and barriers, and thus requires consideration for a different sustainability strategy. CONCLUSIONS: This study is the first international study that relates the sustainability outcomes of translational research project to specific barriers and enablers, and develops an evidence-based framework which provides practical advice on how to ensure the sustainability of health interventions.

IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040.

AIM: To produce current estimates of the national, regional and global impact of diabetes for 2015 and 2040. METHODS: A systematic literature review was conducted to identify data sources on the prevalence of diabetes from studies conducted in the period from 1990 to 2015. An analytic hierarchy process was used to select the most appropriate studies for each country, and estimates for countries without data were modelled using extrapolation from similar countries that had available data. A logistic regression model was used to generate smoothed age-specific estimates, which were applied to UN population estimates. RESULTS: 540 data sources were reviewed, of which 196 sources from 111 countries were selected. In 2015 it was estimated that there were 415 million (uncertainty interval: 340-536 million) people with diabetes aged 20-79years, 5.0 million deaths attributable to diabetes, and the total global health expenditure due to diabetes was estimated at 673 billion US dollars. Three quarters (75%) of those with diabetes were living in low- and middle-income countries. The number of people with diabetes aged 20-79years was predicted to rise to 642 million (uncertainty interval: 521-829 million) by 2040. CONCLUSION: Diabetes prevalence, deaths attributable to diabetes, and health expenditure due to diabetes continue to rise across the globe with important social, financial and health system implications.

The Diabetic Retinopathy Barometer Study: Global perspectives on access to and experiences of diabetic retinopathy screening and treatment.

AIM: To assess the level of awareness, prevention and treatment of Diabetic Eye Disease (DED) comprising Diabetic Retinopathy (DR) and Diabetic Macula Edema (DME) retinopathy among adults with diabetes and health professionals. METHODS: The Diabetic Retinopathy Barometer Study consisted of a qualitative study, which consisted of semi-structured interviews, and a quantitative study using online surveys for adults with diabetes and for health professionals. RESULTS: A total of 4340 adults with diabetes and 2329 health professionals participated in the surveys. Diabetic eye disease (DED) without macular edema (DME) was reported by 19.5% of adults with diabetes and a further 7.6% reported that they had DME. Although 94% of adults with diabetes saw a health care professional for their diabetes, only 79% had ever had an eye examination for DED, and 23% had not had an eye examination in the last year. Moreover, 65% of the ophthalmologists surveyed reported that most patients presented when visual problems had already occurred. Overall, 62% of people with DED had received treatment. Of these, 74% had laser therapy, 29% surgery and 24% anti-VEGF therapy. CONCLUSION: Strategic investment is required to enhance patient education and professional training on the importance of regular eye examinations; and in providing accessible DR screening programmes and proactive treatments.

Susceptibility to IDDM in a Chinese population. Role of HLA class II alleles.

MHC associations with IDDM in a Chinese population were studied to investigate genetic susceptibility to the disorder. The frequency of HLA-DR3 was significantly higher in the diabetic patients (19/49 [38.7%] vs. control subjects, 11/105 [10.5%], Pc less than 1.3 x 10(-3), RR = 5.3 [CI 2.3-12.1]), whereas DR4 was not (11/49 [22.4%] vs. 28/105 [26.7%], NS). The frequency of DR3/4 heterozygosity was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 0/105 [0%], P = 1.7 x 10(-3), RR = 31.5 [CI 3.8-263.6]). The frequency of DR3/9 heterozygosity also was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 2/105 [1.9%], P = 0.03, RR = 6.2 [CI 3.0-12.7]). No significant associations were noted between DQB1 alleles and IDDM. Among DR4-positive subjects, the frequency of DQB1 allele DQB1*0302 was higher in the diabetic patients (10/11 [90.0%] vs. control subjects, 12/24 [50%], Pc less than 0.05, RR = 7.0 [CI 1.3-38.0]), and the frequency of DQB1*0401 was significantly lower in the diabetic patients (2/11 [18.2%] vs. control subjects, 16/24 [66.7%], Pc = 0.04, RR = 0.1 [CI 0.02-0.46]). No DR4 subtype was associated significantly with IDDM. The frequency of DQA1*0501, a DQA1 allele, was higher in diabetic patients (22/41 [53.7%] vs. control subjects, 20/95 [21.1%], Pc less than 3 x 10(-3), RR = 4.3 [CI 2.0-9.3]). The frequency of DQA1*0301, which has been associated consistently with IDDM in other ethnic groups, was not significantly higher in the diabetic patients in this study (27/41 [65.9%] vs. control subjects, 53/95 [55.8%], NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of evening alcohol consumption on next-morning glucose control in type 1 diabetes.

OBJECTIVE: Alcohol is associated with acute hypoglycemia in patients with type 1 diabetes. After drinking alcohol in the evening, delayed hypoglycemia has also been described, although its cause is unknown. We performed a controlled study to investigate this phenomenon. RESEARCH DESIGN AND METHODS: We admitted six men with type 1 diabetes (aged 19-51 years, HbA(1c) 7.0-10.3%) on two occasions, from 5:00 P.M. to 12:00 noon the following day. They received regular insulin injections before standardized meals, at 6:00 P.M. and 8:00 A.M., and a basal insulin infusion (0.15 mU x kg(-1) x min(-1)) from 11:00 P.M. They drank either dry white wine (0.75 g/kg alcohol) or mineral water at 9:00 P.M. over 90 min. Blood glucose, alcohol, insulin, cortisol, growth hormone, and glucagon levels were measured. RESULTS: Blood ethanol reached a mean (SEM) peak of 19.1 (1.2) mmol/l and was undetectable by 8:00 A.M. There were no significant differences in evening or overnight blood glucose levels between the studies. In the morning, fasting and postprandial blood glucose levels were significantly lower after consumption of wine (postprandial peak 8.9 [1.7] vs. 15 [1.5] mmol/l, P < 0.01), and from 10:00 A.M., five subjects required treatment for hypoglycemia (nadir 1.9-2.9 mmol/l). None of the subjects had hypoglycemia after consumption of water. After consumption of wine, growth hormone secretion was significantly reduced between midnight and 4:00 A.M. (area under the curve 2.1 [1.1] vs. 6.5 [2.1] microg. l(-1) x h(-1), P = 0.04). There were no differences in insulin or other hormone levels. CONCLUSIONS: In type 1 diabetes, moderate consumption of alcohol in the evening may predispose patients to hypoglycemia after breakfast the next morning. This is associated with reduced nocturnal growth hormone secretion. Patients should be informed of this risk and advised regarding appropriate preventative measures.

An investigation of Japanese subjects maps susceptibility to type 1 (insulin-dependent) diabetes mellitus close to the DQA1 gene.

Insulin-dependent diabetic and control subjects of Japanese origin were HLA-DRB1, -DQB1, and -DQA1 typed using restriction fragment length polymorphism analysis and sequence-specific oligonucleotide gene probing. The DQA1 allele DQA1*0301 was positively associated with the disease [48/52 (92%) diabetic patients versus 44/64 (69%) control subjects, Pc less than 0.03, RR = 4.97]. Alleles of the DRB1 and DQB1 genes showed no significant association with the disease. The frequency of DQB1 genotypes encoding the amino acid aspartic acid at position 57 of the DQ beta chain did not differ significantly between subjects with insulin-dependent diabetes mellitus (IDDM) and controls. These findings suggest that a susceptibility allele for IDDM in the Japanese is more closely associated with the DQA1 gene than the DQB1 gene.

The influence of HLA-DR and -DQ alleles on progression to multiple sclerosis following a clinically isolated syndrome.

A 5-year follow-up study was performed on 70 Caucasian patients presenting with isolated neurological syndromes of the optic nerve, brain stem, or spinal cord to assess the risk of progression to MS. The influence on patient prognosis of HLA-DR and -DQ alleles and presentation with disseminated brain lesions, demonstrated by MRI scanning, was determined. Clinical progression to MS was observed in 61% of optic neuritis patients, 50% of patients with a brain-stem syndrome, and 35% of patients with a spinal cord disturbance. MS and the isolated clinical syndromes were positively associated with DRB1*1501, DQA1*0102, and DQB1*0602; the frequency of these alleles in the latter group was intermediate between that seen in MS patients and healthy controls. Conversion to MS was positively associated with the DRB1*1501.DQA1*0102.DQB1*0602 haplotype, but the influence of HLA was only significant in patients with disseminated brain lesions at presentation (MRI positive); MS developed in 86% of MRI-positive, DRB1*1501-positive patients compared with 55% of MRI-positive, DRB1*1501-negative patients (p < 0.025). The data suggest that these HLA alleles are involved in susceptibility to initial demyelinating lesion formation and are important in the subsequent development of MS in MRI-positive patients.

An investigation of the association between HLA-DQ heterodimers and type 1 (insulin-dependent) diabetes mellitus in five racial groups.

The association between HLA-DQ alpha Arg52-HLA-DQ beta non-Asp57 heterodimers and type 1 (insulin-dependent) diabetes was compared in Japanese, Chinese, Caucasian, North Indian Asian, and Afro-Caribbean patients to determine their importance in disease susceptibility. The potential to encode four Arg52-non-Asp57 DQ heterodimers, two in cis and two in trans, was significantly associated with increased risk of type 1 diabetes in all races except the Japanese. The possibility of encoding two Arg52-non-Asp57 heterodimers was also significantly associated with increased risk of the disease in all races except the Japanese. The possibility of encoding one heterodimer was not significantly associated with type 1 diabetes in any of the races studied. Heterogeneity testing revealed significant differences in RR values for four, two, and one heterodimers in all races except the Japanese and significant differences in RR for four and two heterodimers when compared across the races. This, together with the lack of an association between Arg52-non-Asp57 heterodimers and type 1 diabetes in the Japanese, suggests that, assuming the same genetic basis for disease in all races, the heterodimer is unlikely to be of primary importance in susceptibility to the disease.

Analysis of a Chinese population suggests that the TNFB gene is not a susceptibility gene for Graves' disease.

Graves' disease is associated with different HLA genes in different races. The TNFB gene lies between the class I and class II HLA genes and has two alleles, TNFB*1 and TNFB*2. Studies in Caucasians have suggested that the TNFB gene might be a susceptibility gene for Graves' disease. To investigate further the role of TNFB in predisposition to Graves' disease, we determined whether the TNFB disease associations in the Chinese were similar to those in Caucasians. A total of 57 patients with Graves' disease (32 male) were studied. A TNFB gene fragment was amplified from genomic DNA by using the polymerase chain reaction and digested with Nco I to distinguish the TNFB alleles (TNFB*1 and TNFB*2). Genotype frequencies were compared with those in a racially matched group of 92 controls. TNFB*1 homozygosity occurred in 15 (26%) Graves' and 22 (24%) control subjects. TNFB*1/TNFB*2 heterozygosity occurred in 29 (51%) and 48 (52%) and TNFB*2 homozygosity in 13 (23%) and 22 (24%), respectively (NS). There were gender differences in the frequencies of TNFB*1 homozygosity (13 male [41%], 2 female [8%]). TNFB*1/TNFB*2 heterozygosity (13 male [41%], 16 female [64%]) (chi 2 = 7.3, p = 0.02), and TNFB*2 frequency (19 male [59%], 23 female [92%]; pc = 0.04) in Graves' patients. We conclude that the TNFB associations with Graves' disease in the Hong Kong Chinese differ between the genders and from those described in Caucasians. The TNFB gene is not a susceptibility gene for Graves' disease.

Genetic susceptibility to multiple sclerosis in a Shanghai Chinese population. The role of the HLA class II genes.

The association of MS with the HLA class II loci DR and DQ was investigated in subjects of Shanghai Chinese and British Caucasian origin. Our aim was to determine whether common alleles predispose to the disease in both races. In the Caucasian population MS was significantly positively associated with the putative haplotype DRB1*1501, DQA1*0102, DQB1*0602. In contrast, HLA class II alleles were not found to predispose to the disease in the Shanghai Chinese, suggesting that this haplotype is unlikely to be a universal susceptibility determinant. The absence of a disease association with the HLA-DR and -DQ genes in the Chinese population has a number of possible explanations. Our study suggests that other genetic and/or environmental components may be more important in determining susceptibility to MS in this race.

The Bgl II RFLP associated with type 1 diabetes in DR3-positive subjects is not due to a DQA1 promoter region polymorphism.

Type 1 (insulin-dependent) diabetes is strongly associated with the HLA genes encoding DR3 and DR4 and their associated DQ alleles. While 70% of all Caucasian diabetic patients carry the DR3-associated allele DQA1*0501, this allele also occurs in up to 40% of the healthy population. A DQA1 Bgl II 7.2 kb RFLP has been shown to identify a disease-associated subset of DR3-positive subjects. We examined the frequency of this RFLP pattern in 43 diabetic and 25 control DR3-positive subjects and found it to be present in 27 (65%) and 5 (20%) respectively (p = 0.0012). The promoter of the DR3-associated DQA1*0501 allele was amplified in four diabetic subjects who were positive, and four control subjects who were negative, for the 7.2 kb band. The promoter was digested with Bgl II to determine whether polymorphism within the promoter created a disease-associated Bgl II restriction site, which might influence disease susceptibility by an effect on gene transcription. No amplified promoter fragment contained a Bgl II restriction site, suggesting that the disease-associated 7.2 kb band does not result from DQA1 promoter region polymorphism but may be due to polymorphism elsewhere on the DR3 haplotype.

Computer-assisted venous occlusion plethysmography in the diagnosis of acute deep venous thrombosis.

Suspicion of deep venous thrombosis (DVT) is a common reason for acute medical admission. The clinical diagnosis is difficult, and thus significant numbers are investigated and found to be normal. Provision of 24-h radiology is costly, and there may be a delay in investigation. We assessed computer-assisted venous occlusion plethysmography as a screening test for DVT, compared with standard radiology. The test has the advantage of being performed on the ward and if reliable would significantly reduce the number of radiological investigations required. We enrolled 215 consecutive patients presenting with the possible diagnosis of DVT, of whom 144 had technically adequate plethysmography results. Plethysmography had a sensitivity of 96% (95%CI 88-99%) and a negative predictive value of 97% (95%CI 91-99%). Patients excluded because of technically inadequate results were older (by a mean 7 years, p=0. 003). Computer-assisted venous occlusion plethysmography is a non-invasive method of rapidly screening for DVT which may be safely used as an initial screening test. The test is less useful in older patients, or patients unable to keep still for a period of 2 min.

Abnormal blood pressure response to exercise in normoalbuminuric insulin dependent diabetic patients.

Eight male normoproteinuric Type I (insulin dependent) diabetic patients and eight age- and sex-matched non-diabetic control subjects were studied for their response to exercise. Systolic blood pressure showed an exaggerated response to exercise in the diabetic group (median 123, range 98-151 mmHg, pre-exercise vs. 187, 163-217 mmHg, immediately post exercise P less than 0.01) compared to the control group (median 112 (100-145) pre-exercise, 153 (138-178) post exercise). Resting noradrenaline levels were lower in the diabetic (D) compared with the control (C) group (D: 1.66, 0.55-3.92 nmol/l vs. C: 2.96, 2.04-4.49 nmol/l, P less than 0.02). Levels rose during exercise by 79% (25-307%) and 43% (4-90%) respectively (NS). Resting urinary sodium was raised in the diabetic group and fell during exercise (P less than 0.05) (D: 146, 74-244 mumol/min, C: 108.5 (83.4-151.0) pre-exercise vs. D: 73, 48-264 mumol/min, C: 81.7 (23.0-92.0) post exercise). Resting atrial natriuretic peptide levels were lower in the diabetic group (D: 10.1, 4.3-16.9 pmol/l vs. C: 16.0, 9.5-22.9 pmol/l, P less than 0.02) and levels rose significantly in both groups during exercise (D: 25.9, 5.2-38.9 pmol/l vs. C: 28.6, 17.3-47.2 pmol/l, P less than 0.05). We conclude that exercise provokes an exaggerated rise in systolic blood pressure and decrease in urinary sodium excretion in normoalbuminuric diabetic patients. These findings may reflect increased sensitivity to the renin-angiotensin-aldosterone system. Reduced atrial natriuretic peptide levels may stimulate sodium retention and increased blood pressure in early diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Performance of a continuous glucose monitoring system during controlled hypoglycaemia in healthy volunteers.

It has been suggested that the continuous glucose monitoring system may be a useful tool for detecting unrecognised hypoglycaemia, especially at times when finger prick testing is difficult or impossible (e.g., at night). Studies suggest that subcutaneous glucose levels closely mimic blood glucose levels with a lag time of only a few minutes. However, no studies have been published to show how well the sensor performs during sustained or in recovery from hypoglycaemia. This study involved using a hyperinsulinaemic glucose clamp (60 mU/m2) in nine healthy volunteers. Each subject had two sensors inserted the day before the study. Blood glucose levels were maintained at euglycaemia for the first 60 min, then decreased to 45 mg/dL (2.5 mmol/L) for 60 min, and finally restored to euglycaemia. Blood glucose measurements were compared with interstitial values recorded by the sensor. Sensor profiles showed acceptable agreement with blood glucose levels at each of the three plateaus with a correlation coefficient of 0.79, slope of 0.85, and mean absolute error of 7%. The sensor drop closely matched the drop in blood glucose, but the recovery from hypoglycaemia was delayed by an average of 26 min. Continuous glucose sensing provides a useful means of detecting unrecognised hypoglycaemia in type 1 diabetes, although the duration of hypoglycaemia may be overestimated.

Impaired absorption and omission of insulin: a novel method of detection using the diabetes advisory system computer model.

The Diabetes Advisory System (DIAS) is a decision-support program developed to assist insulin dose adjustment in type 1 diabetes. In this paper, we show how it might be used to identify impaired absorption or omission of insulin in patients with poorly controlled blood glucose. An evaluation of glucose results from four outpatients with persistent hyperglycemia is presented (age 19-48 years with type 1 diabetes for 13-18 years of duration, HbA1c 9.4-13.6%). Each had completed a 4-day record of blood glucose (BG, pre-meal and bedtime), dietary (carbohydrate) intake, and insulin doses (with injection sites). From these data, DIAS modeled a glucose profile (simulated glucose, SG) for the same period. Qualitative assessments were made of differences between BG and SG, and selective reduction or complete removal of insulin doses where BG >> SG. Large improvements in modeling were attributed to either impaired absorption or omission of insulin. Confirmation of these problems was sought from the patients by detailed consultation and physical examination. Impaired insulin absorption was suspected in two patients, both having significant injection site abnormalities. Insulin omission was suspected in the other two subjects. Both had normal injection sites, and one admitted to missing doses. Following retraining, data from three patients showed noticeable improvements in overall modeling as well as glucose control. Using DIAS in the evaluation of patients with type 1 diabetes may highlight previously unrecognized injection site abnormalities or insulin dose omission. This could assist rational optimization of insulin therapy in cases of persistently poor glucose control.

Increased urinary transferrin excretion in exercising normoalbuminuric insulin-dependent diabetic patients.

The median rate of urinary transferrin excretion is greatly increased by exercise in subjects with uncomplicated type 1 (insulin-dependent) diabetes. This increase is proportionally far greater than that seen in urinary albumin excretion rate after the same exercise. Non-diabetic control subjects showed no rise in urinary transferrin excretion rate following exercise. N-acetyl-beta-D-glucosaminidase excretion rate was higher in diabetic than control groups but did not rise with exercise. Our results suggest that patients with apparently uncomplicated diabetes have abnormal renal function. In this group an elevated urinary transferrin excretion rate appears to be a more sensitive indicator of altered renal function than is elevated albumin excretion rate. The mechanism underlying exercise-induced urinary loss of transferrin remains to be elucidated.

Dynamic updating in DIAS-NIDDM and DIAS causal probabilistic networks.

Diabetes advisory system (DIAS) is a decision support system, which has been developed to provide advice on the amount of insulin injected by subjects with insulin-dependent diabetes mellitus (IDDM). DIAS employs a temporal causal probabilistic network (CPN) to implement a stochastic model of carbohydrate metabolism. The CPN network has recently been extended to provide also advice to subjects with noninsulin-dependent diabetes mellitus (NIDDM). However, due to increased complexity and size of the extended CPN the calculations became unfeasible. The CPN network was, therefore, simplified and a novel approach employed to generate conditional probability tables. The principles of dynamic CPN's were adopted and, in combination with the method of conditioning, learning, and forecasting, were implemented in a time- and memory-efficient way. An evaluation using experimental data was carried out to compare the original and revised DIAS implementations employing data collected by patients with IDDM, and to assess the a posteriori identifiability of model parameters in patients with NIDDM.

DiasNet--a diabetes advisory system for communication and education via the internet.

Intensive diabetes treatment can lead to a substantial reduction of the rate of the complications associated with diabetes. However, a number of patients may have poor control despite specialist care, and this along with devolution of care to non-specialists suggests that alternative interventions should be developed. The present paper describes an Internet based system where more emphasis is put on patient empowerment, the keywords being education and communication. The DiasNet system is based on a well documented decision support system, Dias, designed for use by clinicians. The scope of DiasNet has been widened from being used by clinicians to give advice on insulin dose, to also being used by patients as a tool for education and communication. Patients can experiment with their own data, adjusting insulin doses or meal sizes. In this way different therapeutic and dietary alternatives can be tried out, allowing the patient to gain experience in achieving glycaemic control. DiasNet is implemented in JAVA according to the client/server principle, enabling a new way of communication between patient and clinician: in case of any problems, the patient simply phones the clinician, who immediately, using his or her office PC, can take a look at the data the patient has entered.

Analysing the hypoglycaemic counter-regulation: a clinically relevant phenomenon?

This paper describes an analysis of the temporal relation between episodes of low blood glucose (hypoglycaemia) and counter-regulations, i.e., episodes of elevated blood glucose (hyperglycaemia), in patients with insulin dependent diabetes. The relation was assessed by statistical methods based on a metabolic computer model of the human glucose metabolism. The study material was standard collected clinical data on meals, insulin injections, and measured blood glucose from hospitalised patients. We have found that a typical hypoglycaemic counter-regulation begins 6-8 h after the hypoglycaemia, that it lasts 16-18 h, giving a total duration of 24 h, and that it elevates the blood glucose by 4-10 mmol/l. The phenomenon was demonstrated in the data from more than half of the patients with hypoglycaemic episodes.