The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia, based on important research findings from large cardiovascular outcomes trials published in 2019. Important changes include: 1) the decision to treat high-risk individuals with a glucagon-like peptide 1 (GLP-1) receptor agonist or sodium-glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), cardiovascular death, or chronic kidney disease (CKD) progression should be considered independently of baseline HbA1c or individualized HbA1c target; 2) GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with the presence of specific indicators of high risk; and 3) SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE, and CVD death, as well as in patients with type 2 diabetes with CKD (estimated glomerular filtration rate 30 to ≤60 mL min-1 [1.73 m]-2 or urinary albumin-to-creatinine ratio >30 mg/g, particularly >300 mg/g) to prevent the progression of CKD, hHF, MACE, and cardiovascular death.

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Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

The study group.

Background: Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus The quality of the scientific evidence supporting the use of these assays varies substantially

Approach: An expert committee drafted evidence-based recommendations for the use of laboratory analysis in patients with diabetes An external panel of experts reviewed a draft of the guidelines, which were modified in response to the reviewers’ suggestions A revised draft was posted on the Internet and was presented at the AACC Annual Meeting in July, 2000 The recommendations were modified again in response to oral and written comments The guidelines were reviewed by the Professional Practice Committee of the American Diabetes Association

Content: Measurement of plasma glucose remains the sole diagnostic criterion for diabetes Monitoring of glycemic control is performed by the patients, who measure their own plasma or blood glucose with meters, and by laboratory analysis of glycated hemoglobin The potential roles of noninvasive glucose monitoring, genetic testing, autoantibodies, microalbumin, proinsulin, C-peptide, and other analytes are addressed

Summary: The guidelines provide specific recommendations based on published data or derived from expert consensus Several analytes are of minimal clinical value at the present time, and measurement of them is not recommended

/pdf/guidelines-and-recommendations-for-laboratory-analysis-in-547km3houz.pdf

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61375-1.pdf

Cushing's syndrome

Objective: The aim was to formulate clinical practice guidelines for acromegaly. Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Conclusions: Using an evidence-based approach, this acromegaly guideline addresses impor...

/pdf/acromegaly-an-endocrine-society-clinical-practice-guideline-21g8xh5e8c.pdf

Acromegaly: An Endocrine Society Clinical Practice Guideline

OBJECTIVE We aimed to study the effect of biosynthetic growth hormone (GH) replacement in growth hormone deficient adults. DESIGN We performed a double-blind placebo-controlled cross-over study of 6 months biosynthetic GH, replacement and 6 months placebo separated by a 1-month's washout period. PATIENTS Fourteen growth hormone deficient adults were studied. MEASUREMENTS We measured total body weight, percentage fat mass, lean body mass, muscle volume, exercise capacity, maximum oxygen consumption, muscle strength, bone mineral content, a number of biochemical parameters, IGF-I, GH antibodies and psychological well-being. RESULTS Total body weight remained unchanged, but lean body mass increased (before GH mean +/- SEM 49.8 +/- 5.5, after 53.4 +/- 5.6 kg; placebo before 51.2 +/- 5.4, after 50.4 +/- 5.1 kg; P less than 0.05 and fat mass decreased (before GH 21.5 +/- 4.1, after 19.3 +/- 4.3; placebo before 19.3 +/- 4.0, after 22.5 +/- 4.5 kg; P less than 0.05). Thigh muscle volume increased: (before GH 94.1 +/- 7.7, after 99.5 +/- 8.4 ml; placebo before 99.3 +/- 8.6, after 95.4 +/- 7.8 ml/0.8 mm computerized tomographic slice; P less than 0.05). Exercise capacity increased (before GH 174 +/- 15, after 199 +/- 18.9 watts; placebo before 162.5 +/- 2.3, after 154 +/- 19.8 watts; P less than 0.05), as did maximum oxygen consumption (before GH 1.93 +/- 0.2, after 2.17 +/- 0.2 l/m; placebo before 1.92 +/- 0.3, after 1.98 +/- 0.2 l/m; P less than 0.05). There was no change in quadriceps muscle strength. Alkaline phosphatase increased (before GH 87.5 (32-158), after 106.0 (49-179) U/I, placebo 99.5 (50-145), after 72.0 (40-111) U/I; P less than 0.05) without a change in the spinal bone density. IGF-I increased (before GH 62 (36-97), after 216 (62-362) micrograms/l; placebo before 59 (52-112), after 60.5 (38-94) micrograms/l; P less than 0.05). Carbohydrate tolerance remained unchanged as did fasting lipids, serum sodium, potassium, urea, calcium, phosphate and liver transaminases. Psychological well-being remained unchanged. No growth hormone antibodies were detected before or after GH treatment. CONCLUSIONS GH alters the body composition of growth hormone deficient adults and leads to improved exercise capacity; alkaline phosphatase activity increases but without a change in spinal bone density, and carbohydrate tolerance remains unaltered.

Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study.

OBJECTIVE —The objective of this study was to assess the impact of active versus usual monitoring of algorithmic insulin titration and point-of-care (POC) versus laboratory HbA 1c (A1C) measurement on glycemic control in primary care. RESEARCH DESIGN AND METHODS —The Glycemic Optimization with Algorithms and Labs at Point of Care (GOAL A1C) study was a 24-week, randomized, parallel-group, four-arm, open-label study of 7,893 adults with type 2 diabetes uncontrolled by oral antidiabetic agents and requiring insulin. Patients were randomly assigned by investigators from 2,164 sites in the U.S. to insulin glargine with either 1 ) usual (no unsolicited contact between visits) insulin titration using a simple algorithm with laboratory A1C testing, 2 ) usual titration with POC A1C testing, 3 ) active (weekly monitored) titration with laboratory A1C testing, or 4 ) active titration with POC A1C testing. Outcome measures included a change in A1C and fasting self-monitoring of blood glucose (SMBG) levels, percentage of patients achieving A1C RESULTS —Significant A1C and SMBG reductions were observed in all arms ( P P P P P P CONCLUSIONS —In a predominantly primary care setting, addition of insulin glargine using a simple algorithm achieved significant improvements in glycemic control in patients with type 2 diabetes in all four study arms. Active titration resulted in significant incremental improvements in glycemic control, and, among patients receiving active titration, POC A1C testing resulted in a greater portion achieving A1C

https://care.diabetesjournals.org/content/diacare/29/1/1.full.pdf

Impact of Active Versus Usual Algorithmic Titration of Basal Insulin and Point-of-Care Versus Laboratory Measurement of HbA1c on Glycemic Control in Patients With Type 2 Diabetes The Glycemic Optimization with Algorithms and Labs at Point of Care (GOAL A1C) trial

Summary
OBJECTIVE We assessed the endocrine outcome after transsphenoidal surgery for Cushing's disease.

DESIGN Five-year (mean) follow-up (range 1 month-12 years) of patients undergoing transsphenoidal surgery for Cushing's disease between 1977 and 1990; review of case notes, current clinical and biochemical assessment including 24-hour urinary free cortisol.

SETTING Northern Ireland.

SUBJECTS Forty-one patients (33F:8M); mean age at dlagnosls 39 1 years (9–72 years).

MAIN OUTCOME MEASURES Measurements of early post-operative 0800 h serum cortisol and 24-hour urinary free cortisol at least 24 hours after withdrawal of oral hydrocortisone therapy. This was followed by low dose dexamethasone testing. Current 24-hour urinary free cortisol measurements. Retrospective definition of cure.

RESULTS Twenty-seven patients were either cured or improved by surgery, 14 were considered definite failures.

Of 19 patients cured, eight had unmeasurable early postoperatlve 0800 h serum cortisol levels while of 15 tested, 13 had complete suppression with dexamethasone and two suppressed normally but to still measurable levels (39 and 60 nmol/l respectively). Seventeen patients in total have subsequently had bilateral adrenalectomy of whom two have developed Nelson's syndrome. Seven of the 41 patients were shown to have definite cyclical cortisol secretlon first diagnosed post-operatively in three patients. Hormone deficiency included TSH (5), LH/FSH (1), cortisol (1) and ADH (temporary in 7, permanent in 1). In all, seven patients had some type of permanent hormonal deficiency post-operatively.

CONCLUSIONS Transsphenoidal surgery offers a worthwhile cure rate without the necessity of life-long endocrine therapy. Post-operative endocrine assessment must be rigorous so that early further management can be planned in the significant percentage of patients in whom cure is not achieved. Early complete suppression on low dose dexamethasone testing is very suggestive of cure but repeated and long-term monitoring of 24-hour urinary free cortisol is advisable.

Assessment of endocrine function after transsphenoidal surgery for Cushing's disease

Diabetic peripheral neuropathy and its late sequelae cost >$4 billion annually in the U.S. (1). Improved glycemic control, early detection, and preventive care can prevent or delay adverse outcomes (2–4). An annual foot exam, which may include monofilament testing, is recommended by the American Diabetes Association (5). Unfortunately, neuropathy screening is underutilized in primary care practice (6,7). The GOAL A1C (Glycemic Optimization with Algorithms and Labs At Po1nt of Care) study assessed methods of A1C testing and insulin titration monitoring strategies in a large nationwide sample of predominantly primary care patients with type 2 diabetes. At baseline, physician perception of the presence of neuropathy was assessed via a survey before monofilament testing. A comparison between physician perception and monofilament testing is reported.

GOAL A1C was a randomized, open-label, parallel, four-arm study that compared the impact of point of care versus laboratory A1C testing and weekly versus less frequent insulin titration monitoring on glycemic control in patients with type 2 diabetes adding insulin glargine to existing oral antidiabetic therapy. Eligible patients were aged ≥18 years, inadequately controlled on oral antidiabetic agents (A1C >7.0%), and candidates for insulin. All signed informed consent …

https://care.diabetesjournals.org/content/diacare/28/6/1480.full.pdf

Underdiagnosis of Peripheral Neuropathy in Type 2 Diabetes

Purpose: To investigate the incidence of radiotherapy (RT)-induced central and primary hypothyroidism regarding total dose, fractionation, and adjuvant chemotherapy. Methods and Materials: We retrospectively reviewed the data from 312 patients treated with RT for extracranial head-and-neck tumors between 1964 and 2000. The cervical lymph nodes were irradiated in 197 patients. The radiation doses to the thyroid gland and hypothalamic-pituitary axis were estimated by reconstructing the treatment plans. Results: Clinical central hypothyroidism (CH) was observed in 17 patients (5.4%); the median clinical latency was 4.8 years. Clinical primary hypothyroidism (PH) was observed in 40 patients (20.3%); the median clinical latency was 3.1 years. Multivariate analysis of clinical CH revealed that fractionation, adjuvant chemotherapy, and total dose to the pituitary were not significant. Multivariate analysis of clinical PH revealed that the total dose to the thyroid ( p = 0.043) was significant, but adjuvant chemotherapy, age, and gender were not. Of the patients tested for hypopituitarism, 14 (20.3%) of 69 demonstrated subclinical CH and 17 (27.4%) of 62 demonstrated subclinical PH. The 5-year and 10-year rates of freedom from clinical CH and PH were 97% and 87% and 68% and 67%, respectively. Of the patients tested, the 5-year and 10-year rates of freedom from subclinical CH and PH were 91% and 78% and 71% and 71%, respectively. Conclusion: Clinical and subclinical manifestations of late radiation toxicity were observed in the thyroid and hypothalamic-pituitary axis. Although CH did not indicate a dependence on fractionation, adjuvant chemotherapy, or total dose to the pituitary, PH showed a dependence on the total dose to the thyroid gland.

Laurence Kennedy

Papers

Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study.

Impact of Active Versus Usual Algorithmic Titration of Basal Insulin and Point-of-Care Versus Laboratory Measurement of HbA1c on Glycemic Control in Patients With Type 2 Diabetes The Glycemic Optimization with Algorithms and Labs at Point of Care (GOAL A1C) trial

Assessment of endocrine function after transsphenoidal surgery for Cushing's disease

Underdiagnosis of Peripheral Neuropathy in Type 2 Diabetes

Primary and central hypothyroidism after radiotherapy for head-and-neck tumors.