Brittle diabetes revisited: a description of erratic and difficult-to-control diabetes in an elderly woman with Type 1 diabetes.

BACKGROUND: 'Brittle diabetes' is frequently attributed to psychological stressors causing insulin omission in young women with Type 1 diabetes. It has received little attention in the recent medical literature. CASE REPORT: We report the case of an 87-year-old woman who had recurrent episodes of unexplained diabetic ketoacidosis. Despite frequent inpatient monitoring of capillary glucose, her blood glucose levels remained erratic. She experienced a total of 12 episodes of ketoacidosis (some occurring during hospitalization), with 11 episodes occurring over a 3-month period. Several episodes of ketoacidosis required care in a high-dependency unit and up to 32 h of intravenous insulin and fluids. Extensive investigations failed to identify any underlying cause of the recurrent ketoacidosis. Ultimately, the introduction of a continuous subcutaneous insulin infusion pump resulted in improved glycaemic control and avoided the need for further hospitalizations. CONCLUSION: Individuals of advanced age can benefit from insulin pump therapy. The original definition of 'brittle diabetes' referred to patients whose lives were 'constantly disrupted by episodes of hypo- or hyperglycaemia'. Our case reminds us that this clinical entity can result from altered biology and is not always related to psychological stressors.

Behaviour change in diabetes: behavioural science advancements to support the use of theory.

Behaviour is central to the management of diabetes, both for people living with diabetes and for healthcare professionals delivering evidence-based care. This review outlines the evolution of behavioural science and the application of theoretical models in diabetes care over the past 25 years. There has been a particular advancement in the development of tools and techniques to support researchers, healthcare professionals and policymakers in taking a theory-based approach, and to enhance the development, reporting and replication of successful interventions. Systematic guidance, theoretical frameworks and lists of behavioural techniques provide the tools to specify target behaviours, identify why ideal behaviours are not implemented, systematically develop theory-based interventions, describe intervention content using shared terminology, and evaluate their effects. Several examples from a range of diabetes-related behaviours (clinic attendance, self-monitoring of blood glucose, retinal screening, setting collaborative goals in diabetes) and populations (people with type 1 and type 2 diabetes, healthcare professionals) illustrate the potential for these approaches to be widely translated into diabetes care. The behavioural science approaches outlined in this review give healthcare professionals, researchers and policymakers the tools to deliver care and design interventions with an evidence-based understanding of behaviour. The challenge for the next 25 years is to refine the tools to increase their use and advocate for the role of theoretical models and behavioural science in the commissioning, funding and delivery of diabetes care.

Improving Outcomes Among Young Adults with type 1 diabetes: The D1 Now Randomised Pilot Study Protocol.

BACKGROUND: Young adults (18-25 years old) living with type 1 diabetes mellitus often have sub-optimal glycaemic levels which can increase their risk of long term diabetes complications. Informed by health psychology theory and using a (public and patient involvement) young adult-centred approach, we have developed a complex intervention, entitled D1 Now, to improve outcomes in this target group. The D1 Now intervention includes three components; 1) a support-worker, 2) an interactive messaging system and 3) an agenda setting tool for use during clinic consultations. AIMS: The aim of the D1 Now pilot study is to gather and analyse acceptability and feasibility data to allow us to (1) refine the D1 Now intervention, and (2) determine the feasibility of a definitive Randomised Control Trial (RCT) of the intervention. METHODS: Diabetes clinics on the island of Ireland will be recruited and randomised to a D1 Now intervention arm or a usual care control arm. For a participant to be eligible they should be 18-25 years old and living with type 1 diabetes for at least 12 months. Participant outcomes (influenced by a Core Outcome Set) include change in HbA1c, clinic attendance, number of episodes of severe hypoglycaemia and of diabetic ketoacidosis, diabetes distress, self-management, quality of life and perceived level of control over diabetes; these will be will be measured at baseline and after 12 months follow-up for descriptive statistics only. An assessment of treatment fidelity, a health economic analysis and a qualitative sub-study will also be incorporated into the pilot study. ISRCTN (ref: ISRCTN74114336).

Barriers and facilitators to attendance at Type 2 diabetes structured education programmes: a qualitative study of educators and attendees.

AIMS: Attendance at structured diabetes education has been recommended internationally for all people with Type 2 diabetes. However, attendance rates are consistently low. This qualitative study aimed to explore experiences of attending and delivering Type 2 diabetes structured education programmes in Ireland and barriers and facilitators to attendance. METHODS: People with Type 2 diabetes who had attended one of the three programmes delivered in Ireland and educators from the three programmes took part in semi-structured telephone interviews. Interviews were audio-taped, transcribed and analysed using inductive thematic analysis. RESULTS: Twelve attendees and 14 educators were interviewed. Two themes were identified in relation to experiences of programme attendance and delivery: 'Structured education: addressing an unmet need' and 'The problem of non-attendance'. The third theme 'Barriers to attendance: can't go, won't go, don't know and poor system flow' outlined how practicalities of attending, lack of knowledge of the existence and benefits, and limited resources and support for education within the diabetes care pathway impacts on attendance. The final theme 'Supporting attendance: healthcare professionals and the diabetes care pathway' describes facilitators to participants' attendance and the strategies educators perceived to be important in increasing attendance. CONCLUSIONS: Healthcare professionals have an important role in improving attendance at structured diabetes education programmes. Improving attendance may require promotion by healthcare professionals and for education to be better embedded and supported within the diabetes care pathway.

The preferences of young adults with Type 1 diabetes at clinics using a discrete choice experiment approach: the D1 Now Study.

AIM: Attending routine outpatient clinic appointments is a central self-management behaviour of individuals living with Type 1 diabetes. A large number of young adults with Type 1 diabetes disengage from diabetes services, which may contribute to poor psychosocial and diabetes outcomes. The aim of this study is to elicit preferences from young adults with Type 1 diabetes regarding clinic-related services to inform service delivery. METHODS: A discrete choice experiment was developed to understand the preferences of young adults with Type 1 diabetes for clinic-related services. RESULTS: Young adults recruited from young adult Type 1 diabetes clinics in 2016 completed the experiment (n = 105). Young adults with Type 1 diabetes showed a preference for shorter waiting times, seeing a nurse and a consultant, relative to a nurse alone, and a flexible booking system compared with fixed appointment times. Results suggest no preference for a nurse and a doctor, relative to a nurse alone, or other optional services (e.g. seeing dietitians or psychologists), type of HbA1c test and digital blood glucose diaries over paper-based diaries. CONCLUSION: This study highlights aspects of routine clinic appointments that are valued by young adults living with Type 1 diabetes, namely shorter waiting times at clinic, the option to see both a nurse and consultant at each visit and a flexible clinic appointment booking system. These findings suggest young adults with Type 1 diabetes value convenience and should help services to restructure their clinics to be more responsive to the needs of young adults.

Factors influencing health-related quality of life in patients with Type 1 diabetes.

AIMS: Generic, preference-based measures of health-related quality of life (HRQoL) are a common input to the economic evaluation of new health technologies. As such, it is important to explore what characteristics of patients with Type 1 diabetes might impact scores on such measures. METHODS: This study utilizes baseline data from a cluster-randomized trial that recruited patients with Type 1 diabetes at six centers across Ireland. Health-related quality of life was assessed using the three-level EuroQol EQ-5D (EQ-5D) measure. Patients' responses to individual dimensions of the EQ-5D were explored. To see which patient factors influenced EQ-5D scores, multivariate regression analysis was conducted with EQ-5D scores as the outcome variable. RESULTS: Data was available for 437 Type 1 diabetes patients. The median age of these patients was 40 (IQR: 31-49) years and 53.8% were female. Overall, patients reported a high HRQoL based on EQ-5D scores (0.87 (SD: 0.19). Fifty-four percent of patients reported a perfect HRQoL. For those that reported problems, the most common dimension was the anxiety/depression dimension of the EQ-5D (29.6%). In the multivariate regression analysis, self-reported mental illness (- 0.22 (95% CI: -0.34, - 0.10)) and being unemployed (- 0.07 (95% CI: -0.13, - 0.02)) were negatively associated with EQ-5D scores (p < 0.05). The influence of self-reported mental illness was persistent in sensitivity analyses. CONCLUSIONS: The study results indicate that patients with Type 1 diabetes report a high HRQoL based on responses to the EQ-5D. However, there are a substantial number of Type 1 diabetes patients that report problems in the anxiety/depression dimension, which may provide avenues to improve patients' HRQoL. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79759174 .

A systematic review of interventions to improve outcomes for young adults with Type 1 diabetes.

BACKGROUND: Many young adults with Type 1 diabetes experience poor outcomes. The aim of this systematic review was to synthesize the evidence regarding the effectiveness of interventions aimed at improving clinical, behavioural or psychosocial outcomes for young adults with Type 1 diabetes. METHODS: Electronic databases were searched. Any intervention studies related to education, support, behaviour change or health service organizational change for young adults aged between 15-30 years with Type 1 diabetes were included. A narrative synthesis of all studies was undertaken due to the large degree of heterogeneity between studies. RESULTS: Eighteen studies (of a possible 1700) were selected and categorized: Health Services Delivery (n = 4), Group Education and Peer Support (n = 6), Digital Platforms (n = 4) and Diabetes Devices (n = 4). Study designs included one randomized controlled trial, three retrospective studies, seven feasibility/acceptability studies and eight studies with a pre/post design. Continuity, support, education and tailoring of interventions to young adults were the most common themes across studies. HbA1c was the most frequently measured outcome, but only 5 of 12 studies that measured it showed a significant improvement. CONCLUSION: Based on the heterogeneity among the studies, the effectiveness of interventions on clinical, behavioural and psychosocial outcomes among young adults is inconclusive. This review has highlighted a lack of high-quality, well-designed interventions, aimed at improving health outcomes for young adults with Type 1 diabetes.

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison.

AIMS: Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. METHODS: Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. RESULTS: Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. CONCLUSION: These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.

Providing diabetes patients with personalized written clinical information in the diabetes outpatient clinic: a pilot study.

AIM: To explore the impact of sharing personalized written clinical information with diabetes outpatients on patient involvement in the clinical consultation. METHODS: One hundred and six patients attending diabetes outpatient clinics for a review visit were allocated to receive either a patient information sheet containing personalized clinical information (prior to their consultation) or no information sheet. Both groups were compared by observing the number of patients raising any of the 17 topics included on the patient information sheet, the number of topics raised by each individual and the proportion of the total consultation time in which the patient was involved in conversation. A mean patient score was calculated by summing the number of topics raised by each patient. RESULTS: Patients in the intervention group were more likely to initiate a conversation on all 17 topics during the consultation than those in the control group. These differences were significant for all topics except glycated haemoglobin (HbA(1c)) and diabetes complications. The mean patient score was significantly higher in the intervention group (5 vs. 1, P < 0.005), with the highest patient score in the intervention group being 14 compared with 4 in the control group. The mean patient conversation time for the intervention group was significantly longer than for the control group (6.34 vs. 3.34 min, P < 0.01). The overall consultation time did not significantly differ between groups. CONCLUSIONS: Providing patients with personalized clinical information in a routine clinical setting can increase patients' involvement in the consultation without significantly increasing the length of the consultation.

Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans.

Insulin concentrations in humans continuously change and typically increase only when glucose also increases such as with eating. In this setting, it is not known whether the severity of hepatic and extrahepatic insulin resistance is comparable and whether the ability of glucose to regulate its own uptake and release is defective in non-insulin-dependent diabetes mellitus (NIDDM). To address this question, NIDDM and nondiabetic subjects were studied when glucose concentrations were clamped at either 5 mM (euglycemia) or varied so as to mimic the glucose concentrations observed in nondiabetic humans after food ingestion (hyperglycemia). Insulin was infused so as to simulate a "nondiabetic" postprandial profile. During euglycemia, insulin increased glucose disposal in nondiabetic but not diabetic subjects indicating marked extrahepatic resistance. In contrast, insulin-induced suppression of glucose release was only minimally less (P < 0.05) in diabetic than nondiabetic subjects (-1.06 +/- 0.09 vs. -1.47 +/- 0.21 nmol.kg-1 per 4 h). Hyperglycemia substantially enhanced disposal in both groups. Glucose effectiveness measured as the magnitude of enhancement of disposal (0.59 +/- 0.18 vs. 0.62 +/- 0.17 nmollkg-1 per 4 h) and suppression of release (-0.36 +/- 0.12 vs. -0.14 +/- 0.12 nmol.kg-1 per 4 h) did not differ in the diabetic and nondiabetic subjects. In conclusion, when assessed in the presence of a physiological insulin profile, people with NIDDM demonstrate: (a) profound extrahepatic insulin resistance, (b) modest hepatic insulin resistance, and (c) normal ability of glucose to stimulate its own uptake and suppress its own release.

Investigating the management of diabetes in nursing homes using a mixed methods approach.

AIMS: As populations age there is an increased demand for nursing home (NH) care and a parallel increase in the prevalence of diabetes. Despite this, there is growing evidence that the management of diabetes in NHs is suboptimal. The reasons for this are complex and poorly understood. This study aimed to identify the current level of diabetes care in NHs using a mixed methods approach. METHODS: The nursing managers at all 44 NHs in County Galway in the West of Ireland were invited to participate. A mixed methods approach involved a postal survey, focus group and telephone interviews. RESULTS: The survey response rate was 75% (33/44) and 27% (9/33) of nursing managers participated in the qualitative research. The reported prevalence of diagnosed diabetes was 14% with 80% of NHs treating residents with insulin. Hypoglycaemia was reported as 'frequent' in 19% of NHs. A total of 36% of NHs have staff who have received diabetes education or training and 56% have access to diabetes care guidelines. Staff education was the most cited opportunity for improving diabetes care. Focus group and interview findings highlight variations in the level of support provided by GPs and access to dietetic, podiatry and retinal screening services. CONCLUSIONS: There is a need for national clinical guidelines and standards of care for diabetes management in nursing homes, improved access to quality diabetes education for NH staff, and greater integration between healthcare services and NHs to ensure equity, continuity and quality in diabetes care delivery.

Strength in Numbers: an international consensus conference to develop a novel approach to care delivery for young adults with type 1 diabetes, the D1 Now Study.

PLAIN ENGLISH SUMMARY: Many young adults with type 1 diabetes struggle with the day-to-day management of their condition. They often find it difficult to find the time to attend their clinic appointments and to meet with their diabetes healthcare team. Young adults living with type 1 diabetes are not routinely involved in research that may help improve health services other than being invited to take part in studies as research participants. A 3-day international conference was held in Galway in June 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". It aimed to bring together people from a broad variety of backgrounds with an interest in young adults with type 1 diabetes. Young people with type 1 diabetes came together with healthcare professionals, researchers, software developers and policy makers to come up with and agree on a new approach for engaging young adults with type 1 diabetes with their health services and to improve how they manage their diabetes.The people involved in the conference aimed to reach agreement (consensus) on a fixed set of outcome measures called a core outcome set (COS) that the group would recommend future studies involving young adults with type 1 diabetes to use, to suggest a new approach (intervention) for providing health services to young adults with type 1 diabetes, and to come up with health technology ideas that could help deliver the new intervention. Over the 3 days, this diverse international group of people that included young adults living with type 1 diabetes, agreed on a COS, 3 key parts of a new intervention and 1 possible health technology idea that could help with how the overall intervention could be delivered.Involving young adults living with type 1 diabetes in a 3-day conference along with other key groups is an effective method for coming up with a new approach to improve health services for young adults with type 1 diabetes and better support their self-management. ABSTRACT: Background A 3-day international consensus meeting was hosted by the D1 Now study team in Galway on June 22-24, 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". The aim of the meeting was to bring together young adults with type 1 diabetes, healthcare providers, policy makers and researchers to reach a consensus on strategies to improve engagement, self-management and ultimately outcomes for young adults living with type 1 diabetes. Methods This diverse stakeholder group participated in the meeting to reach consensus on (i) a core outcome set (COS) to be used in future intervention studies involving young adults with type 1 diabetes, (ii) new strategies for delivering health services to young adults and (iii) potential digital health solutions that could be incorporated into a future intervention. Results A COS of 8 outcomes and 3 key intervention components that aim to improve engagement between young adults with type 1 diabetes and service providers were identified. A digital health solution that could potentially compliment the intervention components was proposed. Conclusion The outputs from the 3-day consensus conference, that held patient and public involvement at its core, will help the research team further develop and test the D1 Now intervention for young adults with type 1 diabetes in a pilot and feasibility study and ultimately in a definitive trial. The conference represents a good example of knowledge exchange among different stakeholders for health research and service improvement.

The impact of sharing personalised clinical information with people with type 2 diabetes prior to their consultation: A pilot randomised controlled trial.

AIM: To assess the impact of sharing personalised clinical information with people with type 2 diabetes prior to their out-patient consultation on patient involvement during the consultation, diabetes self-management self-efficacy and glycaemic control. METHODS: A pilot three-arm randomised controlled trial. The 'intervention booklet' group received a booklet including personalised clinical information, a 'general information booklet' control group received a booklet with no personalised clinical information and a 'usual care' control group received no written information. RESULTS: 136 people took part. The intervention group were significantly more likely to have shown the booklet to a 'significant other', (48% V 23%, p<0.05), brought the booklet with them to the clinic (85% V 35%, p<0.005) and to refer to the booklet during the consultation (45% V 13%, p<0.005). No significant differences in patient involvement during the consultation, diabetes management self-efficacy or glycaemic control were found between the three groups. CONCLUSIONS: Although participants found it useful to receive their clinical results, no differences were found in the patient outcomes measured. PRACTICE IMPLICATIONS: Further pilot work on the timing of the intervention, who it is targeted at and what outcomes are measured is warranted before proceeding to a full-scale RCT.

Assessment of hepatic sensitivity to glucagon in NIDDM: use as a tool to estimate the contribution of the indirect pathway to nocturnal glycogen synthesis.

NIDDM is associated with excessive rates of endogenous glucose production in both the postabsorptive and postprandial states. To determine whether this is due to an intrinsic increase in hepatic sensitivity to glucagon, 9 NIDDM and 10 nondiabetic subjects were studied on three occasions. On each occasion, glycogen was labeled the evening before the study with subjects ingesting meals containing [6-3H]galactose. Beginning at 6:00 A.M. on the following morning, somatostatin was infused to inhibit endogenous hormone secretion. Insulin concentrations were maintained constant at basal levels (defined as that necessary to keep glucose at approximately 5 mmol/l) in each individual. On one occasion, glucagon was infused at a rate of 0.65 ng x kg(-1) x min(-1) throughout the experiment, resulting in glucagon concentrations of approximately 130 pg/ml and a slow but comparable fall in endogenous glucose production with time in both groups. On the other two occasions, the glucagon infusion was increased at 10:00 A.M. to either 1.5 or 3.0 ng x kg(-1) x min(-1), resulting in an increase in glucagon concentrations to approximately 180 and 310 pg/ml, respectively. The increment in endogenous glucose production (i.e., area above basal) did not differ in diabetic and nondiabetic subjects during either the 1.5 ng x kg(-1) x min(-1) (0.75 +/- 0.055 vs. 0.78 +/- 0.048 mmol/kg) or 3.0 ng x kg(-1) x min(-1) (1.06 +/- 0.066 vs. 1.10 +/- 0.073 mmol/kg) glucagon infusions. In contrast, the amount of [6-3H]glucose released from glycogen was lower (P < 0.05) in the diabetic than nondiabetic subjects during both glucagon infusions. The specific activity of glycogen, calculated as the integrated release of [6-3H]glucose divided by the integrated release of unlabeled glucose, was lower (P < 0.05) in diabetic subjects than in nondiabetic subjects during both the 1.5 ng x kg(-1) x min(-1) (19.0 +/- 3.9 vs. 41.4 +/- 5.7 dpm/micromol) and 3.0 ng x kg(-1) x min(-1) (19.1 +/- 3.1 vs. 36.5 +/- 7.2 dpm/micromol) glucagon infusions, implying that a greater portion of the glucose released from glycogen was derived from the indirect pathway. We concluded that although NIDDM is not associated with an intrinsic alteration in hepatic sensitivity to glucagon, it does alter the relative contributions of the direct and indirect pathways to nocturnal glycogen synthesis.

The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature.

OBJECTIVES: To critically analyze the literature linking microalbuminuria with total and cardiovascular mortality and cardiovascular morbidity in non-insulin-dependent diabetes mellitus (NIDDM) and to quantify the risk. METHODS: A combination of retrieval techniques (MEDLINE, SCISEARCH, and handsearching published bibliographies) was used to find all relevant articles based on title and abstract and "Methods" sections. Unpublished data on albumin excretion rate were sought from large NIDDM cohort studies. RESULTS: A total of 264 citations were retrieved, of which 11 cohort studies were selected for inclusion in the overview, representing a total of 2138 patients followed up for a mean of 6.4 years. Patient age was similar across cohorts. Duration of NIDDM ranged from newly diagnosed to 13 years. The prevalence of microalbuminuria ranged from 20% to 36% in the 8 cohorts that excluded patients with clinical proteinuria. All studies reported either a trend or a significant association between microalbuminuria and total mortality or cardiovascular morbidity or mortality; the overall odds ratio for death was 2.4 (95% confidence interval, 1.8-3.1) and for cardiovascular morbidity or mortality, 2.0 (95% confidence interval, 1.4-2.7). We found no evidence of reporting bias. CONCLUSION: Microalbuminuria is a strong predictor of total and cardiovascular mortality and cardiovascular morbidity in patients with NIDDM.

Fish oil supplementation in type 2 diabetes: a quantitative systematic review.

OBJECTIVE: To determine the effects of fish oil supplementation on lipid levels and glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A comprehensive search of Medline, Embase, Lilacs, the Cochrane Clinical Trials Registry bibliographies of relevant papers, and expert input updated through September 1998 was undertaken. All randomized placebo-controlled trials were included in which fish oil supplementation was the only intervention in subjects with type 2 diabetes. Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. Eighteen trials including 823 subjects followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day The outcomes studied were glycemic control and lipid levels. RESULTS: Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil on lowering triglycerides (-0.56 mmol/l [95% CI -0.71 to -0.41]) and raising LDL cholesterol (0.21 mmol/l [0.02 to 0.41]). No statistically significant effect was observed for fasting glucose. HbA1c total cholesterol, or HDL cholesterol. The triglyceride-lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited hypertriglyceridemic subjects and used higher doses of fish oil. Heterogeneity was observed and explained by the recruitment of subjects with baseline hypertriglyceridemia in some studies. CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, raises LDL cholesterol, and has no statistically significant effect on glycemic control. Trials with hard clinical end points are needed.

The role of growth hormone in the development of diabetic retinopathy.

OBJECTIVE: To determine the role of growth hormone (GH) in the development of diabetic retinopathy. RESEARCH DESIGN AND METHODS: Medical records of 1,423 patients who had undergone insulin tolerance tests (1976-1991) at the Mayo Clinic were examined, and diabetic subjects were identified as either GH-deficient (GH increment after hypoglycemia < 5 micrograms/L and peak < 10 micrograms/L) or GH-sufficient. Prevalence of retinopathy was determined in these cases and in a cohort group of diabetic subjects selected to match the GH-deficient cases. These control patients (32 cases) were selected from medical records of individuals who had received medical care at Mayo during the same interval but who had not undergone insulin tolerance testing. RESULTS: Twenty-four patients with diabetes were identified, of whom 16 were GH-deficient and 8 GH-sufficient. Despite comparable age, duration of diabetes, and metabolic control, the prevalence of diabetic retinopathy in the GH-deficient group (2 of 16; 12.5%) was less (P < 0.05) than that observed in the GH-sufficient group (5 of 8; 62.5%). Prevalence in the GH-deficient group also was lower than that observed in the cohort control group (15 of 32, 47%). CONCLUSIONS: These data strongly suggest that GH contributes to the development of diabetic retinopathy in humans.

Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the Heart Outcomes Prevention Evaluation Study. The HOPE Study Investigators.

OBJECTIVE: To describe the characteristics of diabetic and nondiabetic participants in the Heart Outcomes Prevention Evaluation (HOPE) Study who are at high risk of developing cardiovascular (CV) disease and who have microalbuminuria (MA), and to identify the key determinants of MA in these two groups. RESEARCH DESIGN AND METHODS: Albuminuria was measured in 97% of patients enrolled in the HOPE Study as part of the MICRO-HOPE (MA, CV, and Renal Outcomes in HOPE) substudy. Baseline clinical characteristics of diabetic and nondiabetic participants with MA were recorded, and the univariate and multivariate relationship between these characteristics and the presence of MA was estimated for both groups. RESULTS: Baseline urinary albumin determinations were available in 3,574 (97.8%) diabetic participants and 5,708 (97.0%) nondiabetic participants. MA was detected in 1,151 (32.2%) diabetic participants and 837 (14.7%) nondiabetic participants. Age, waist-to-hip ratio, diabetes, smoking, hypertension, vascular disease, and left ventricular hypertrophy were independent determinants of MA in all participants. In diabetic participants, the odds of MA increased 16% for every 10.4 years of diabetes duration, and increased 8% for every 0.9% increase in glycated hemoglobin (assuming a GHb assay with an upper limit of 6% in the nondiabetic range). CONCLUSIONS: MA is independently associated with several risk factors for CV and renal disease in both diabetic and nondiabetic individuals at high risk for CV disease.

Effects of changing diagnostic criteria on the risk of developing diabetes.

OBJECTIVE: The American Diabetes Association (ADA) has recommended that the fasting plasma glucose (FPG) level used to diagnose diabetes be changed from 7.8 mmol/l (the level recommended by the National Diabetes Data Group [NDDG] in 1979) to 7.0 mmol/l. We examined the impact of this change on rates of progression to overt diabetes from different levels of FPG. RESEARCH DESIGN AND METHODS: Using the laboratory database of Mayo Clinic, we assembled a cohort of 8,098 nondiabetic Olmsted County residents 40 years of age or older on 1 July 1983. Subjects were followed for a median of 9 years. RESULTS: Among 7,567 individuals with follow-up FPG data, 778 (10.3%) progressed to ADA diabetes and 513 (6.8%; P < 0.0001) progressed to NDDG diabetes. The risk of developing ADA diabetes was 7, 19, and 39% for individuals with initial FPG values in the ranges of <5.6, 5.6-6.0, and 6.1-6.9 mmol/l, respectively. For progression to NDDG diabetes, the respective risks were 3, 11, and 25%. A clear gradient of risk was observed within the "normal" range of FPG (<5.6 mmol/l). Among the 793 individuals who developed ADA diabetes, 222 (29%) developed NDDG diabetes simultaneously and 291 (37%) developed NDDG diabetes later. In all FPG subgroups, progression to ADA diabetes occurred approximately 7 years sooner than progression to NDDG diabetes. CONCLUSIONS: The baseline level of FPG is a major predictor of an individual's risk of developing diabetes. The proposed change in the diagnostic criteria for diabetes will lead to earlier diagnosis among individuals who are destined to develop the disease.