Robert A. Vigersky

OBJECTIVE: To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and The Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice. PARTICIPANTS: Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The sponsors had no input into the development of or content of the report. EVIDENCE: The writing group considered data from recent clinical trials and other studies to update the prior workgroup report. Unpublished data were not used. Expert opinion was used to develop some conclusions. CONSENSUS PROCESS: Consensus was achieved by group discussion during conference calls and face-to-face meetings, as well as by iterative revisions of the written document. The document was reviewed and approved by the American Diabetes Association's Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society's Clinical Affairs Core Committee in October 2012 and by Council in November 2012. CONCLUSIONS: The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes, reviewed the implications of hypoglycemia on both short- and long-term outcomes, considered the implications of hypoglycemia on treatment outcomes, presented strategies to prevent hypoglycemia, and identified knowledge gaps that should be addressed by future research. In addition, tools for patients to report hypoglycemia at each visit and for clinicians to document counseling are provided.

OBJECTIVE Continuous glucose monitoring (CGM) has provided new measures of glycemic control that link to diabetes complications. This study investigated the association between the time in range (TIR) assessed by CGM and diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS A total of 3,262 patients with type 2 diabetes were recruited. TIR was defined as the percentage of time spent within the glucose range of 3.9–10.0 mmol/L during a 24-h period. Measures of glycemic variability (GV) were assessed as well. DR was determined by using fundus photography and graded as 1) non-DR; 2) mild nonproliferative DR (NPDR); 3) moderate NPDR; or 4) vision-threatening DR (VTDR). RESULTS The overall prevalence of DR was 23.9% (mild NPDR 10.9%, moderate NPDR 6.1%, VTDR 6.9%). Patients with more advanced DR had significantly less TIR and higher measures of GV (all P for trend <0.01). The prevalence of DR on the basis of severity decreased with ascending TIR quartiles (all P for trend <0.001), and the severity of DR was inversely correlated with TIR quartiles (r = −0.147; P < 0.001). Multinomial logistic regression revealed significant associations between TIR and all stages of DR (mild NPDR, P = 0.018; moderate NPDR, P = 0.014; VTDR, P = 0.019) after controlling for age, sex, BMI, diabetes duration, blood pressure, lipid profile, and HbA1c. Further adjustment of GV metrics partially attenuated these associations, although the link between TIR and the presence of any DR remained significant. CONCLUSIONS TIR assessed by CGM is associated with DR in type 2 diabetes.

BACKGROUND: There has been recent recognition of the limitations of hemoglobin A1C (HbA1C) in describing both short- and long-term glycemic control. Continuous glucose monitoring (CGM) provides robust data about short-term glycemic control and provides metrics such as percent time-in-range (%TIR) that are now routinely reported to describe the change in glycemic control after an intervention in a clinical study or a change in therapy in a patient's care. Recent studies have shown that %TIR may have similar associations with diabetes microvascular complications as does HbA1C. The relationship of %TIR to the long-standing metric of overall glycemic control has not been clearly defined to date. METHODS: Articles that report paired HbA1C and %TIR metrics (n = 1137) or HbA1C and frequent self-monitoring of blood glucose (SMBG) (n = 1440) across a wide range of HbA1Cs, technologies, and subject demographics were reviewed to determine the correlation of these metrics. RESULTS: = 0.71). This relationship did not change after excluding one study that used SMBG or six studies with ≤7 days of CGM. For every absolute 10% change in %TIR, there was a 0.8% (9 mmol/mol) change in HbA1C. CONCLUSIONS: There is a good correlation between HbA1C and %TIR that may permit the transition to %TIR as the preferred metric for determining the outcome of clinical studies, predicting of the risk of diabetes complications, and assessing of an individual patient's glycemic control.

OBJECTIVE: To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and The Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice. PARTICIPANTS: Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The sponsors had no input into the development of or content of the report. EVIDENCE: The writing group considered data from recent clinical trials and other studies to update the prior workgroup report. Unpublished data were not used. Expert opinion was used to develop some conclusions. CONSENSUS PROCESS: Consensus was achieved by group discussion during conference calls and face-to-face meetings, as well as by iterative revisions of the written document. The document was reviewed and approved by the American Diabetes Association's Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society's Clinical Affairs Core Committee in October 2012 and by Council in November 2012. CONCLUSIONS: The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes, reviewed the implications of hypoglycemia on both short- and long-term outcomes, considered the implications of hypoglycemia on treatment outcomes, presented strategies to prevent hypoglycemia, and identified knowledge gaps that should be addressed by future research. In addition, tools for patients to report hypoglycemia at each visit and for clinicians to document counseling are provided.

We tested hypothalamic, pituitary and endocrine function in 19 patients with secondary amenorrhea associated with simple weight loss who did not have anorexia nervosa to evaluate the effects of weight loss on these systems. Thermoregulation at 10 degrees C and 49 degrees C was abnormal and correlated with the percentage below ideal body weight (r = 0.62, P less than 0.02, and r = 0.55, P less than 0.05, respectively). Partial diabetes insipidus was found in 27 per cent of patients with simple weight loss. They had delayed peak plasma luteinizing hormone levels after 10 microgram of luteinizing-hormone-releasing factor, which was correlated with percentage below ideal body weight (r = 0.49, P less than 0.05). Delayed peak plasma thyrotropin levels after 500 microgram of thyrotropin-releasing factor were found. No prolactin, pituitary, thyroid or adrenal abnormalities were present. These findings are qualitatively similar to results of studies in 29 patients with anorexia nervosa, but less severe and less frequently present. We conclude that hypothalamic dysfunction may be caused by weight loss per se.