Proximal Renal Artery Stenosis Presenting as Uncontrolled Hypertension.

Presentation: We present a case of 50-year-old lady who present with 1-month history of uncontrolled hypertension. Diagnosis: Magnetic resonance angiography showed stenosis of the left renal artery just beyond the ostium extending over approximately 7mm in length. Computed tomography angiography show focal narrowing of the proximal renal artery just distal to vessel origin, approximately 60% stenosis. Treatment: Anti-hypertensive medication was initiated in the ward. She was referred to vascular surgeon for renal bypass. Discussion: Renal artery stenosis is common cause of hypertension but may go unrecognised. The focus of this case is on the evaluation and necessity for a complete evaluation of the patient who is presenting with uncontrolled hypertension. To rule out renal artery stenosis, patient should be examined using CT-angiography or, if possible, arteriography.

Guidelines for the management of diabetes in care homes during the Covid-19 pandemic.

The National Diabetes Stakeholders Covid-19 Response Group was formed in early April 2020 as a rapid action by the Joint British Diabetes Societies for Inpatient Care, Diabetes UK, the Association of British Clinical Diabetologists, and Diabetes Frail to address and support the special needs of residents with diabetes in UK care homes during Covid-19. It was obvious that the care home sector was becoming a second wave of Covid-19 infection and that those with diabetes residing in care homes were at increased risk not only of susceptibility to infection but also to poorer outcomes. Its key purposes included minimising the morbidity and mortality associated with Covid-19 and assisting care staff to identify those residents with diabetes at highest risk of Covid-19 infection. The guidance was particularly created for care home managers, other care home staff, and specialist and non-specialist community nursing teams. The guidance covers the management of hyperglycaemia by discussion of various clinical scenarios that could arise, the management of hypoglycaemia, foot care and end of life care. In addition, it outlines the conditions where hospital admission is required. The guidance should be regarded as interim and will be updated as further medical and scientific evidence becomes available.

Guidelines for the management of diabetes services and patients during the COVID-19 pandemic.

The UK National Diabetes Inpatient COVID Response Group was formed at the end of March 2020 to support the provision of diabetes inpatient care during the COVID pandemic. It was formed in response to two emerging needs. First to ensure that basic diabetes services are secured and maintained at a time when there was a call for re-deployment to support the need for general medical expertise across secondary care services. The second was to provide simple safe diabetes guidelines for use by specialists and non-specialists treating inpatients with or suspected of COVID-19 infection. To date the group, comprising UK-based specialists in diabetes, pharmacy and psychology, have produced two sets of guidelines which will be continually revised as new evidence emerges. It is supported by Diabetes UK, the Association of British Clinical Diabetologists and NHS England.

Characterizing adults with Type 2 diabetes mellitus and intellectual disability: outcomes of a case-finding study.

AIMS: To report the results of a case-finding study conducted during a feasibility trial of a supported self-management intervention for adults with mild to moderate intellectual disability and Type 2 diabetes mellitus, and to characterize the study sample in terms of diabetes control, health, and access to diabetes management services and support. METHODS: We conducted a cross-sectional case-finding study in the UK (March 2013 to June 2015), which recruited participants mainly through primary care settings. Data were obtained from medical records and during home visits. RESULTS: Of the 325 referrals, 147 eligible individuals participated. The participants' mean (sd) HbA1c concentration was 55 (15) mmol/mol [7.1 (1.4)%] and the mean (sd) BMI was 32.9 (7.9) kg/m2 , with 20% of participants having a BMI >40 kg/m2 . Self-reported frequency of physical activity was low and 79% of participants reported comorbidity, for example, cardiovascular disease, in addition to Type 2 diabetes. The majority of participants (88%) had a formal or informal supporter involved in their diabetes care, but level and consistency of support varied greatly. Post hoc exploratory analyses showed a significant association between BMI and self-reported mood, satisfaction with diet and weight. CONCLUSIONS: We found high obesity and low physical activity levels in people with intellectual disability and Type 2 diabetes. Glycaemic control was no worse than in the general Type 2 diabetes population. Increased risk of morbidity in this population is less likely to be attributable to poor glycaemic control and is probably related, at least in part, to greater prevalence of obesity and inactivity. More research, focused on weight management and increasing activity in this population, is warranted.

Language matters. Addressing the use of language in the care of people with diabetes: position statement of the English Advisory Group.

The language used by healthcare professionals can have a profound impact on how people living with diabetes, and those who care for them, experience their condition and feel about living with it day-to-day. At its best, good use of language, both verbal and written, can lower anxiety, build confidence, educate and help to improve self-care. Conversely, poor communication can be stigmatizing, hurtful and undermining of self-care and can have a detrimental effect on clinical outcomes. The language used in the care of those with diabetes has the power to reinforce negative stereotypes, but it also has the power to promote positive ones. The use of language is controversial and has many perspectives. The development of this position statement aimed to take account of these as well as the current evidence base. A working group, representing people with diabetes and key organizations with an interest in the care of people with diabetes, was established to review the use of language. The work of this group has culminated in this position statement for England. It follows the contribution of Australia and the USA to this important international debate. The group has set out practical examples of language that will encourage positive interactions with those living with diabetes and subsequently promote positive outcomes. These examples are based on a review of the evidence and are supported by a simple set of principles.

Thrombolytic therapy in pulmonary embolism.

Massive pulmonary embolism carries a high mortality. Potential treatment includes anticoagulation, thrombolytic therapy and embolectomy. We report a case of deep vein thrombosis leading to progressive massive pulmonary embolism despite appropriate anticoagulation, where thrombolysis with IVC filter placement resulted in a successful outcome.

A national survey of the current state of screening services for diabetic retinopathy: ABCD-diabetes UK survey of specialist diabetes services 2006.

The main aims were to ascertain the progress made in the implementation of retinal screening services and to explore any barriers or difficulties faced by the programmes. The survey focused on all the essential elements for retinal screening, including assessment and treatment of screen-positive cases. Eighty-five per cent of screening programmes have a coordinated screening service and 73% of these felt that they have made significant progress. Eighty-five per cent of screening units use 'call and recall' for appointments and 73.5% of programmes follow the National Screening Committee (NSC) guidance. Although many units worked closely with ophthalmology, further assessment and management of screen-positive patients was a cause for concern. The fast-track referral system, to ensure timely and appropriate care, has been difficult to engineer by several programmes. This is demonstrated by 48% of programmes having waiting lists for patients identified as needing further assessment and treatment for retinopathy. Ophthalmology service for people with diabetic retinopathy was provided by a dedicated ophthalmologist in 89.4% of the programmes. Sixty-six per cent of the programmes reported inadequate resources to sustain a high-quality service, while 26% highlighted the lack of infrastructure and 49% lacked information technology (IT) support. In conclusion, progress has been made towards establishing a national screening programme for diabetic retinopathy by individual screening units, with a number of programmes providing a structured retinal screening service. However, programmes face difficulties with resource allocation and compliance with Quality Assurance (QA) standards, especially those which apply to ophthalmology and IT support. Screening programmes need to be resourced adequately to ensure comprehensive coverage and compliance with QA.

Diabetes specialist nurses and role evolvement: a survey by Diabetes UK and ABCD of specialist diabetes services 2007.

AIMS: To review the working practices of UK diabetes specialist nurses (DSNs), specific clinical roles, and to examine changes since 2000. METHODS: Postal questionnaires were sent to lead DSNs from all identifiable UK diabetes centres (n = 361). Quantitative and qualitative data were collected on the specific clinical roles, employment, and continual professional development of hospital and community DSNs, Nurse Consultants and Diabetes Healthcare Assistants. RESULTS: 159 centres (44%) returned questionnaires. 78% and 76% of DSNs plan and deliver education sessions compared with 13% in 2000 with a wider range of topics and with less input from medical staff. 22% of DSNs have a formal role in diabetes research compared with 48% in 2000. 49% of Hospital DSNs, 56% of Community DSNs and 66% of Nurse Consultants are involved in prescribing. 55% of DSNs carry out pump training, 72% participate in ante-natal and 27% renal clinics. 90% of services have independent diabetes nurse-led clinics. 93% of services have a dedicated Paediatric DSN. The mean number of children under the care of each PDSN is 109 (mode 120), which exceeds Royal College of Nursing recommendations. 48% of DSNs have protected time for continuing professional development of staff and 15% have a protected budget. One third of DSNs are on short-term contracts funded by external sources. CONCLUSIONS: The DSN role has evolved since 2000 to include complex service provision and responsibilities including specialist clinics, education of healthcare professionals and patients. The lack of substantive contracts and protected study leave may compromise these roles in the future.

Association of British Clinical Diabetologists (ABCD) and Diabetes-UK survey of specialist diabetes services in the UK, 2006. 1. The consultant physician perspective.

AIMS: To identify the views and working practices of consultant diabetologists in the UK in 2006-2007, the current provision of specialist services, and to examine changes since 2000. METHODS: All 592 UK consultant diabetologists were invited to participate in an on-line survey. Quantitative and qualitative analyses of responses were undertaken. A composite 'well-resourced service score' was calculated. In addition to an analysis of all respondents, a sub-analysis was undertaken, comparing localities represented both in 2006/2007 and in 2000. RESULTS: In 2006/2007, a 49% response rate was achieved, representing 50% of acute National Health Service Trusts. Staffing levels had improved, but remained below recommendations made in 2000. Ten percent of specialist services were still provided by single-handed consultants, especially in Northern Ireland (in 50% of responses, P = 0.001 vs. other nations). Antenatal, joint adult-paediatric and ophthalmology sub-specialist diabetes services and availability of biochemical tests had improved since 2000, but access to psychology services had declined. Almost 90% of consultants had no clinical engagement in providing community diabetes services. The 'well-resourced service score' had not improved since 2000. There was continued evidence of disparity in resources between the nations (lowest in Wales and Northern Ireland, P = 0.007), between regions in England (lowest in the East Midlands and the Eastern regions, P = 0.028), and in centres with a single-handed consultant service (P = 0.001). Job satisfaction correlated with well-resourced service score (P = 0.001). The main concerns and threats to specialist services were deficiencies in psychology access, inadequate staffing, lack of progress in commissioning, and the detrimental impact of central policy on specialist services. CONCLUSIONS: There are continued disparities in specialist service provision. Without effective commissioning and adequate specialist team staffing, integrated diabetes care will remain unattainable in many regions, regardless of reconfigurations and alternative service models.

Measurement of proinsulin and intermediates. Validation of immunoassay methods by high-performance liquid chromatography.

Human proinsulin and 32-33 split proinsulin have been measured in the peripheral circulation by immunoradiometric assays (IRMAs) and have been shown to be elevated in impaired glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM). The IRMA for 32-33 split proinsulin did not discriminate between this molecule and des-32 or des-31,32 split proinsulin. We describe the comparison of IRMA for human plasma proinsulin and 32-33 split proinsulins with assays combined with high-performance liquid chromatography (HPLC), which can discriminate between 32-33 split, des-32 split, and des-31,32 split proinsulin. Subjects were those with normal glucose tolerance (n = 8) and those with NIDDM (n = 17), who were studied while fasting and 30 min after a glucose load. After collection, blood was centrifuged promptly, and the serum/plasma was stored frozen until assay. Both IRMA and HPLC methods were calibrated against synthetic peptides. Interassay coefficients of variation for the IRMA for proinsulin and 32-33 split proinsulin were < 13% over the ranges 3.8-65 pmol/l and 6.4-65 pmol/l, respectively. The following regression lines were obtained: proinsulin IRMA = -0.143 + 1.066 HPLC, r = 0.860; 32-33 split proinsulin IRMA = 0.048 + 1.051 HPLC; and des-31,32 split proinsulin, r = 0.814. For both analytes, there was no significant difference in the relationship of IRMA to HPLC results between the various subject groups and various time points. Thus, the IRMA for proinsulin has been validated by an independent method.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups.

OBJECTIVE: To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease. RESEARCH DESIGN AND METHODS: A total of 27 subjects with NIDDM (17 Caucasian, 10 Asian) were given metformin and placebo each for a 12-wk period in a randomized, double-blind, placebo-controlled crossover study, and the dose was increased after 1 and 6 wk, up to a maximum of 850 mg three times a day. Insulin resistance, glycemic control, and cardiovascular risk factors were assessed before and after each treatment phase. The end of 12 wk of metformin treatment was compared with the end of 12 wk of placebo treatment. RESULTS: Metformin treatment was associated with significant improvement in FPG at 6 and 12 wk (mean difference at 12 wk, -3.08 mM, 95% CI -4.12 to -2.04 mM, P < 0.0001) and MCR of glucose (median difference 0.40 ml.kg-1.min-1, interquartile range -0.10 to 1.30 ml.kg-1.min-1, P = 0.036). beta-cell function calculated by HOMA also improved significantly (median difference 14%, interquartile range 7 to 23%, P < 0.001). Total triglyceride (median difference -0.2 mM, interquartile range -0.6 to 0.1 mM, P = 0.034), total cholesterol (mean difference -0.52 mM, 95% CI -0.83 to -0.22 mM, P = 0.002), and LDL cholesterol (mean difference -0.40 mM, 95% CI -0.64 to -0.16 mM, P = 0.002) fell significantly on metformin treatment, whereas no significant changes were observed in HDL cholesterol. PAI-1 activity fell significantly (mean difference -5.3 AU/ml, 95% CI -8.2 to -2.4 AU/ml, P = 0.001), but plasma fibrinogen concentrations and platelet function, spontaneous or agonist induced, were unaffected. UAE was lower on metformin treatment (median difference -2.4 micrograms/min, interquartile range -4.4 to -0.2 micrograms/min, P = 0.004), but metformin had no significant effect on BP. The effects of metformin on glycemic control and cardiovascular risk factors were generally similar in the two ethnic groups. CONCLUSIONS: These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease.

Intact proinsulin, des 31,32 proinsulin, and specific insulin concentrations among nondiabetic and diabetic subjects in populations at varying risk of type 2 diabetes.

OBJECTIVE: To examine hyperinsulinemia, insulin secretion, and beta-cell function in Pima Indians, South Asians, and whites, populations at varying risk of diabetes. RESEARCH DESIGN AND METHODS: We investigated 136 Pima Indian, 98 Asian, and 80 white nondiabetic and 172 Pima Indian, 40 Asian, and 49 white diabetic subjects. Highly specific assays for insulin, intact proinsulin, and des 31,32 proinsulin were used. Insulin secretion was assessed using ratio of increment (0 to 30 min) in insulin to glucose concentrations during an oral glucose tolerance test (OGTT). RESULTS: Nondiabetic Pima Indians were significantly more obese than Asians and whites. Pima Indian subjects had significantly higher (P < 0.01) fasting insulin concentrations (median 109 pmol/l, range 40-250) than Asian (37 pmol/l, range 17-91) and white (30 pmol/l, range 10-82) subjects. These differences remained significant when controlled for obesity. Nondiabetic Pima Indians also had higher fasting C-peptide concentrations and higher early insulin secretion during an OGTT. Fasting concentrations of intact proinsulin and des 31,32 proinsulin were also significantly higher in Pima Indians (P < 0.01). However, the proportion of proinsulin-like molecules was significantly lower (P < 0.01) in Pima Indians (median 7.9% vs. 12.7% for South Asians and 12.2% for whites). Subjects with diabetes from the three ethnic groups showed significantly higher fasting insulin concentrations but lower 30-min insulin and lower ratios of increment (0-30 min) in insulin to glucose concentrations than did nondiabetic subjects. The proportion of proinsulin-like molecules was not significantly different in diabetic subjects from the three ethnic groups. CONCLUSIONS: These specific assays for insulin indicate that after adjusting for obesity nondiabetic Pima Indians are truly hyperinsulinemic, which is consistent with their insulin resistance as measured by other methods. Hyperinsulinemia in this population with a high risk of diabetes is likely to be due to enhanced insulin secretion. Furthermore, in Pima Indians, the predominant beta-cell secretory product is insulin and not its precursors. We conclude that the differences in the risk of diabetes among these three groups are not due to differences in insulin secretion or insulin processing. Subjects with type 2 diabetes have defective early insulin secretion during OGTTs but show fasting hyperinsulinemia even when specific assays for insulin are used.

Hyperinsulinemia in nondiabetic Asian subjects using specific assays for insulin, intact proinsulin, and des-31, 32-proinsulin.

OBJECTIVE: To investigate the contributions of intact proinsulin and of des-31,32-proinsulin to fasting concentrations of insulin-like molecules in nondiabetic subjects from two ethnic groups (Asian and white) and to see whether Asian subjects are hyperinsulinemic compared with white subjects using highly specific assays for insulin. RESEARCH DESIGN AND METHODS: We investigated subjects with normal glucose tolerance (NGT) (82 Asian and 67 white) and impaired glucose tolerance (IGT) (16 Asian and 13 white), diagnosed by using standard World Health Organization criteria. Highly specific monoclonal antibody-based assays were used to measure insulin, intact proinsulin, and des-31,32-proinsulin. An index of insulin secretion was derived as a ratio of incremental insulin to incremental glucose concentrations from 0 to 30 min during an oral glucose tolerance test. RESULTS: Asian subjects with NGT, despite being significantly thinner than whites (BMI 24.4 +/- 3.5 vs. 25.7 +/- 3.7 kg/m2, P = 0.04), had a more central distribution of obesity (subscapsular-to-triceps skinfold ratios 1.36 +/- 0.69 vs. 1.17 +/- 0.41, P = 0.047). Asian subjects with NGT showed significant hyperinsulinemia 2 h after oral glucose load (plasma insulin median 274 pmol/l [range 26-1,505] vs. 186 pmol/l [27-720], P < 0.005) compared with whites. Asian subjects with NGT also had significantly higher insulin increments (P < 0.02) compared with white subjects and significantly higher fasting concentrations of intact proinsulin (median 2.7 pmol/l [range 0.9-14.1] vs. 2.1 [0.8-7.9], P < 0.02) but not of des-31,32-proinsulin. The ratio of proinsulin-like molecules to the total sum of three insulin-like molecules, however, was similar between Asian and white subjects with NGT and IGT. CONCLUSIONS: These results indicate that when specific assays for insulin are used, Asian subjects show postglucose load hyperinsulinemia and fasting hyperproinsulinemia compared with white subjects, suggesting increased insulin secretion and/or the presence of underlying insulin resistance in this ethnic group. The contribution of proinsulin-like molecules to total insulin-like molecules was similar between Asian and white subjects with NGT and IGT, and there was no contribution to hyperinsulinemia in Asian subjects.

Diabetic retinopathy, promoter (4G/5G) polymorphism of PAI-1 gene, and PAI-1 activity in Pima Indians with type 2 diabetes.

OBJECTIVE: To examine the relationship between plasma plasminogen activator inhibitor 1 (PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic retinopathy in Pima Indians with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 171 Pima Indians with type 2 diabetes between the ages of 30-70 years in a population-based epidemiological survey. Plasma PAI-1 activity was measured by a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase chain reaction (PCR) using allele-specific primers. Retinopathy was assessed by ophthalmoscopy after pupillary dilation and classified as any retinopathy or as nonproliferative and proliferative. RESULTS: Retinopathy was present in 70 (41%) subjects, and 4 (2.3%) subjects had proliferative retinopathy. Plasma PAI-1 activity was not significantly different among subjects with and without retinopathy (17.1 +/- vs. 19.7 +/- 9.1 arbitrary units (AU)/ml, P = 0.09). PAI-1 activity was negatively correlated with duration of diabetes (rs = -0.18, P = 0.02). In a logistic regression analysis controlled for age, sex, BMI, and duration of diabetes, any retinopathy was significantly associated with fasting plasma glucose concentrations (P < 0.05), 2-h postload glucose (P = 0.02), and HbA1c (P = 0.008), but not with PAI-1 activity (P = 0.48). The prevalence of retinopathy in the three genotype groups differed significantly (4G/4G, 4G/5G, and 5G/5G were 44, 49, and 24%, respectively; chi 2 = 8.22, df = 2, P = 0.016) and remained significant after controlling for age, sex, BMI, duration of diabetes, glycated hemoglobin, and urine albumin-to-creatine ratio in a logistic regression analysis. The odds ratios for retinopathy in subjects with 4G/4G and 4G/5G, compared with the 5G/5G genotype, were 2.0 and 3.1, respectively. CONCLUSIONS: Although diabetic retinopathy in Pima Indians with type 2 diabetes is not associated with PAI-1 activity, subjects with the 4G/4G and 4G/5G genotype had a higher prevalence of retinopathy compared with 5G/5G PAI-1genotype. These preliminary findings indicate that in Pima Indians with type 2 diabetes, presence of the 4G allele of the PAI-1 gene was associated with a higher risk of diabetic retinopathy.

The relationship of concentrations of insulin and proinsulin-like molecules with coronary heart disease prevalence and incidence. A study of two ethnic groups.

OBJECTIVE: To define the potential role of proinsulin-like molecules as risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS: Fasting concentrations of proinsulin, des-31,32-proinsulin, and insulin, and of insulin 2 h after a 75-g glucose load, were measured in 1,034 nondiabetic europid subjects and 257 south Asian subjects and related to prevalent coronary heart disease (Minnesota-coded electrocardiographic criteria or ischemic chest pain). In 137 south Asian subjects, the fasting concentrations were related to incident coronary heart disease over a 6.5-year follow-up. RESULTS: The standardized odds ratios for prevalent coronary heart disease were as follows: fasting insulin, 1.29 (1.11-1.49), P = 0.0006; 2-h insulin, 1.25 (1.08-1.45), P = 0.003; proinsulin, 1.23 (0.99-1.53), P = 0.058; and des-31,32-proinsulin, 1.32 (1.03-1.69), P = 0.026. The odds ratios were similar in the two ethnic groups. These relationships became insignificant when controlling for age, sex, and BMI. The standardized odds ratios for incident coronary heart disease were as follows: fasting insulin, 0.99 (0.63-1.55), P = 0.97; proinsulin, 1.13 (0.72-1.78), P = 0.59; and des-31,32-proinsulin, 1.00 (0.61-1.63), P = 1.00. CONCLUSIONS: We have found similar relationships between concentrations of proinsulin-like molecules and prevalent coronary heart disease, as are observed for insulin in these nondiabetic subjects, although these molecules comprise only approximately 10% of all insulin-like molecules. It appears biologically implausible that these relationships represent cause and effect.