XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Ju Mei,†,‡,∥ Nelson L. C. Leung,†,‡,∥ Ryan T. K. Kwok,†,‡ Jacky W. Y. Lam,†,‡ and Ben Zhong Tang*,†,‡,§ †HKUST-Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China ‡Department of Chemistry, HKUST Jockey Club Institute for Advanced Study, Institute of Molecular Functional Materials, Division of Biomedical Engineering, State Key Laboratory of Molecular Neuroscience, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China Guangdong Innovative Research Team, SCUT-HKUST Joint Research Laboratory, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China

Aggregation-Induced Emission: Together We Shine, United We Soar!

Accurate measurement of blood pressure is essential to classify individuals, to ascertain blood pressure-related risk, and to guide management. The auscultatory technique with a trained observer and mercury sphygmomanometer continues to be the method of choice for measurement in the office, using the first and fifth phases of the Korotkoff sounds, including in pregnant women. The use of mercury is declining, and alternatives are needed. Aneroid devices are suitable, but they require frequent calibration. Hybrid devices that use electronic transducers instead of mercury have promise. The oscillometric method can be used for office measurement, but only devices independently validated according to standard protocols should be used, and individual calibration is recommended. They have the advantage of being able to take multiple measurements. Proper training of observers, positioning of the patient, and selection of cuff size are all essential. It is increasingly recognized that office measurements correlate poorly with blood pressure measured in other settings, and that they can be supplemented by self-measured readings taken with validated devices at home. There is increasing evidence that home readings predict cardiovascular events and are particularly useful for monitoring the effects of treatment. Twenty-four-hour ambulatory monitoring gives a better prediction of risk than office measurements and is useful for diagnosing white-coat hypertension. There is increasing evidence that a failure of blood pressure to fall during the night may be associated with increased risk. In obese patients and children, the use of an appropriate cuff size is of paramount importance.

/pdf/recommendations-for-blood-pressure-measurement-in-humans-and-19z5w6eq69.pdf

Recommendations for Blood Pressure Measurement in Humans and Experimental Animals Part 1: Blood Pressure Measurement in Humans: A Statement for Professionals From the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research

D iabetes mellitus is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payers, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. Specifically titled sections of the standards address children with diabetes, pregnant women, and people with prediabetes. These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed. For more detailed information about management of diabetes, refer to references 1–3. The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A large number of these interventions have been shown to be cost-effective (4). A grading system (Table 1), developed by the American Diabetes Association (ADA) andmodeled after existingmethods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E. These standards of care are revised annually by the ADA’s multidisciplinary Professional Practice Committee, incorporating new evidence. For the current revision, committee members systematically searched Medline for human studies related to each subsection and published since 1 January 2010. Recommendations (bulleted at the beginning of each subsection and also listed in the “Executive Summary: Standards of Medical Care in Diabetesd2012”) were revised based on new evidence or, in some cases, to clarify the prior recommendation or match the strength of the wording to the strength of the evidence. A table linking the changes in recommendations to new evidence can be reviewed at http:// professional.diabetes.org/CPR_Search. aspx. Subsequently, as is the case for all Position Statements, the standards of care were reviewed and approved by the ExecutiveCommittee of ADA’s Board ofDirectors, which includes health care professionals, scientists, and lay people. Feedback from the larger clinical community was valuable for the 2012 revision of the standards. Readers who wish to comment on the “Standards of Medical Care in Diabetesd2012” are invited to do so at http://professional.diabetes.org/ CPR_Search.aspx. Members of the Professional Practice Committee disclose all potential financial conflicts of interest with industry. These disclosures were discussed at the onset of the standards revisionmeeting. Members of the committee, their employer, and their disclosed conflicts of interest are listed in the “Professional PracticeCommitteeMembers” table (see pg. S109). The AmericanDiabetes Association funds development of the standards and all its position statements out of its general revenues and does not utilize industry support for these purposes.

https://www.science-open.com/document_file/bb04d9d0-b3df-4133-9494-e71e300f4279/PubMedCentral/bb04d9d0-b3df-4133-9494-e71e300f4279.pdf

Standards of Medical Care in Diabetes—2012

D iabetes is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed. For more detailed information about management of diabetes, refer to references 1–3. The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was used to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E. These standards of care are revised annually by the ADA multidisciplinary Professional Practice Committee, and new evidence is incorporated. Members of the Professional Practice Committee and their disclosed conflicts of interest are listed in the Introduction. Subsequently, as with all position statements, the standards of care are reviewed and approved by the Executive Committee of ADA’s Board of Directors.

Standards of Medical Care in Diabetes—2010

Objectives To study the effects of metformin on the incidence of vitamin B-12 deficiency ( Design Multicentre randomised placebo controlled trial. Setting Outpatient clinics of three non-academic hospitals in the Netherlands. Participants 390 patients with type 2 diabetes receiving treatment with insulin. Intervention 850 mg metformin or placebo three times a day for 4.3 years. Main outcome measures Percentage change in vitamin B-12, folate, and homocysteine concentrations from baseline at4, 17, 30, 43, and 52 months. Results Compared with placebo, metformin treatment was associated with a mean decrease in vitamin B-12 concentration of −19% (95% confidence interval −24% to −14%; P 220 pmol/l). Conclusions Long term treatment with metformin increases the risk of vitamin B-12 deficiency, which results in raised homocysteine concentrations. Vitamin B-12 deficiency is preventable; therefore, our findings suggest that regular measurement of vitamin B-12 concentrations during long term metformin treatment should be strongly considered. Trial registration Clinicaltrials.gov NCT00375388.

https://www.bmj.com/content/bmj/340/bmj.c2181.full.pdf

Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial

Results: Metformin treatment prevented weight gain (mean weight gain, �3.07 kg [range, �3.85 to �2.28 kg]; P.001), improved glycemic control (mean reduction in HbA1c level, 0.4% percentage point [95% CI, 0.550.25]; P.001) (where CI indicates confidence interval), despite the aim of similar glycemic control in both groups, and reduced insulin requirements (mean reduction, 19.63 IU/d [95% CI, 24.91-14.36 IU/d]; P.001). Metformin was not associated with an improvement in the primary end point. It was, however, associated with an improvement in the secondary, macrovascular end point (hazard ratio, 0.61 (95% CI, 0.40-0.94; P = .02), which was partly explained by the difference in weight. The number needed to treat to prevent 1 macrovascular end point was 16.1 (95% CI, 9.2-66.6). Conclusions: Metformin, added to insulin in patients with DM2, improved body weight, glycemic control, and insulin requirements but did not improve the primary end point. Metformin did, however, reduce the risk of macrovascular disease after a follow-up period of 4.3 years. These sustained beneficial effects support the policy to continue metformin treatment after the introduction of insulin in any patient with DM2, unless contraindicated. Trial Registration: ClinicalTrials.gov Identifier: NCT00375388

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Long-term Effects of Metformin on Metabolism and Microvascular and Macrovascular Disease in Patients With Type 2 Diabetes Mellitus

Background—A strong but presently unexplained inverse association between blood pressure and insulin sensitivity has been reported. Microvascular vasodilator capacity may be a common antecedent linking insulin sensitivity to blood pressure. To test this hypothesis, we studied 18 normotensive and glucose-tolerant subjects showing a wide range in insulin sensitivity as assessed with the hyperinsulinemic, euglycemic clamp technique. Methods and Results—Blood pressure was measured by 24-hour ambulatory blood pressure monitoring. Videomicroscopy was used to measure skin capillary density and capillary recruitment after arterial occlusion. Skin blood flow responses after iontophoresis of acetylcholine and sodium nitroprusside were evaluated by laser Doppler flowmetry. Insulin sensitivity correlated with 24-hour systolic blood pressure (24-hour SBP; r=−0.50, P<0.05). Capillary recruitment and acetylcholine-mediated vasodilatation were strongly and positively related to insulin sensitivity (r=0.84, P<0.001; r=0.7...

https://www.ahajournals.org/doi/pdf/10.1161/01.CIR.99.7.896

Microvascular function relates to insulin sensitivity and blood pressure in normal subjects

Capillary rarefaction occurs in many tissues in patients with essential hypertension and may contribute to an increased vascular resistance and impaired muscle metabolism. Rarefaction may be caused by a structural (anatomic) absence of capillaries, functional nonperfusion, or both. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of subjects with essential hypertension. We examined skin capillary density with video microscopy before and during maximization of the number of perfused capillaries by venous congestion (structural capillary number) and before and during postocclusive reactive hyperemia (capillary recruitment, which may have a structural and/or functional basis). The study group was composed of 26 patients with never-treated essential hypertension and 26 normotensive control subjects. In both groups, intermittently perfused capillaries in the resting state were an important functional reserve for recruitment during postocclusive hyperemia. Recruitment of perfused capillaries during postocclusive reactive hyperemia was decreased in the hypertensive subjects compared with normotensive control subjects (47.9+/-6.8 versus 55.3+/-8.2 capillaries/mm(2), respectively; P<0.01). During venous occlusion, maximal capillary density was significantly lower in the hypertensive subjects than in the control subjects (52.5+/-6.6 versus 57.2+/-8.6 capillaries/mm(2), respectively; P<0.05), suggesting structural rarefaction. However, in the hypertensive subjects compared with the normotensive subjects, a smaller proportion of the maximal number of capillaries was perfused during postocclusive hyperemia (91.6+/-7.5% versus 97.2+/-2.7%, respectively; P<0.05), suggesting an additional functional impairment of capillary recruitment. If the difference in capillary numbers during venous congestion ( approximately 4.6 capillaries/mm(2)) truly reflects the structural difference between the normotensive and hypertensive subjects, then, at most, 62% (4.6/7.4x100%) of the difference in capillary numbers during postocclusive hyperemia ( approximately 7.4 capillaries/mm(2)) can be explained by structural defects, and at least 38% can be explained by functional defects. In conclusion, in patients with essential hypertension, recruitment of perfused capillaries is impaired, which can be explained by both functional and structural rarefaction.

Impaired Skin Capillary Recruitment in Essential Hypertension Is Caused by Both Functional and Structural Capillary Rarefaction

In patients with insulin-dependent diabetes mellitus (IDDM), microalbuminuria is a predictor of widespread severe microangiopathy and macroangiopathy. Patients with microalbuminuria show generalized dysfunction of the vascular endothelium, but it is unknown whether endothelial dysfunction precedes the development of microalbuminuria. We examined a cohort of 17 IDDM patients at baseline and on three occasions during a follow-up of (median) 64 months (range 51-89). All had normal (< 15 micrograms/min) urinary albumin excretion (UAE) at the first three examinations. At the fourth examination, 11 patients had normal UAE and 6 had microalbuminuria (median 25.7 micrograms/min [range 15.3-42.8]). Compared with patients with normal UAE, microalbuminuric patients had significantly higher plasma levels of von Willebrand factor (vWF), a marker of endothelial dysfunction, at the second (200% [168-274] vs. 131% [69-186]), third (208% [188-270] vs. 125% [82-190]), and fourth examinations (231% [202-269] vs. 132% [88-208], P < 0.0001), but not at baseline (128% [98-161] vs. 122% [87-210]). An increase in vWF preceded the occurrence of microalbuminuria by approximately 3 years. The groups did not differ with regard to age, diabetes duration, blood pressure, mean glycated hemoglobin and cholesterol, smoking habits, or extent of retinopathy. Endothelial dysfunction, as estimated by plasma vWF concentration, precedes and may predict the development of microalbuminuria in IDDM.

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Ab J.M. Donker

Papers

Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial

Long-term Effects of Metformin on Metabolism and Microvascular and Macrovascular Disease in Patients With Type 2 Diabetes Mellitus

Microvascular function relates to insulin sensitivity and blood pressure in normal subjects

Impaired Skin Capillary Recruitment in Essential Hypertension Is Caused by Both Functional and Structural Capillary Rarefaction

Endothelial Dysfunction Precedes Development of Microalbuminuria in IDDM