Case report: Uncovering hidden glucose patterns in medicated versus unmedicated bipolar disorder and comorbid type 1 diabetes mellitus.

Introduction: Type 1 diabetes mellitus is characterized by an absolute insulin deficiency requiring the lifetime intensive insulin therapy accompanied by daily self-monitoring, self-management, ongoing education, and complex diabetes care. Regular patient-clinician shared therapeutic decisions based on age, sex, comorbidities, medications, predicted impact of meals, physical activity, stress, hormonal changes, insulin therapy, and patterns of glycemic changes are key for achieving glycemic targets. The impact of various phases of bipolar disorder and their treatment on continuous glucose levels remains unexplored and calls for future assessments. Case presentation: The present case reports a 41-year-old Caucasian female with an established diagnosis of bipolar II disorder and type 1 diabetes mellitus who discontinued long-term mood-stabilizing pharmacotherapy with quetiapine. Real-time continuous glucose monitoring performed before and 6-months following the discontinuation of quetiapine revealed hidden glucose patterns in medicated versus unmedicated bipolar disorder. Despite the known adverse metabolic effects of quetiapine, the continuous glucose monitoring captured more stable and near-normal continuous glucose values during the antipsychotic treatment compared to unmedicated stages of bipolar disorder with considerably higher glucose values and glucose variability. Conclusion: The case report highlights the importance of the ongoing psychopharmacotherapy of bipolar disorder in comorbid type 1 diabetes mellitus to reduce mood-induced reactivity, emotional urgency, and non-emotional impulsivity that may contribute to dysglycemia. If not effectively treated, the "bipolar diabetes" is likely to progress to multiple psychiatric and somatic complications. The bidirectional links between the phases of bipolar disorder and the corresponding continuous glucose patterns can help advance clinical decision-making and yield innovative1 research that can translate into efficacious clinical practice.

Factors associated with psychiatric and physical comorbidities in bipolar disorder: a nationwide multicenter cross-sectional observational study.

Background: Bipolar disorder (BD) is a chronic and disabling affective disorder with significant morbidity and mortality. Despite the high rate of psychiatric and physical health comorbidity, little is known about the complex interrelationships between clinical features of bipolar illness and comorbid conditions. The present study sought to examine, quantify and characterize the cross-sectional associations of psychiatric and physical comorbidities with selected demographic and clinical characteristics of adults with BD. Methods: A nationwide multicenter cross-sectional observational epidemiological study conducted from October 2015 to March 2017 in Slovakia. Results: Out of 179 study participants [median age 49 years (interquartile range IQR 38-58); 57.5% females], 22.4% were free of comorbidity, 42.5% had both psychiatric and physical comorbidities, 53.6% at least one psychiatric comorbidity, and 66.5% at least one physical comorbidity. The most prevalent were the essential hypertension (33.5%), various psychoactive substance-related disorders (21.2%), specific personality disorders (14.6%), obesity (14.5%), and disorders of lipoprotein metabolism (14%). The presence of an at least one physical comorbidity, atypical symptoms of BD, and unemployed status were each associated with an at least one psychiatric comorbidity independent of sex, early onset of BD (age of onset <35 years), BD duration and pattern of BD illness progression (p < 0.001). The presence of various psychoactive substance-related disorders, BD duration, atypical symptoms of BD, unemployed status, pension, female sex, and not using antipsychotics were each associated with an at least one physical comorbidity independent of the pattern of BD illness progression (p < 0.001). In several other multiple regression models, the use of antipsychotics (in particular, olanzapine) was associated with a decreased probability of the essential hypertension and predicted the clinical phenotype of comorbidity-free BD (p < 0.05). Conclusion: This cross-national study has reported novel estimates and clinical correlates related to both the comorbidity-free phenotype and the factors associated with psychiatric and physical comorbidities in adults with BD in Slovakia. The findings provide new insights into understanding of the clinical presentation of BD that can inform clinical practice and further research to continue to investigate potential mechanisms of BD adverse outcomes and disease complications onset.

Autogenic Training in Mental Disorders: What Can We Expect?

Autogenic training (AT) is a well-established self-induced relaxation technique based on autosuggestion. From the past two decades, an increasing number of AT studies strongly suggests the practical usefulness of psychophysiological relaxation in the area of medicine. Despite this interest, to date, limited critical clinical reflection on the application and effects of AT in mental disorders exists. The present paper reviews psychophysiological, psychopathological, and clinical aspects of AT in persons with mental disorders with emphasis on implications for future research and practice. Based on a formal literature search, 29 reported studies (7 meta-analyses/systematic reviews) were identified that examined the effects and impact of AT on mental disorders. The main psychophysiological effects of AT include autonomic cardiorespiratory changes paralleled by central nervous system activity modifications and psychological outputs. Studies demonstrate consistent efficacy of AT in reducing anxiety and medium range positive effects for mild-to-moderate depression. The impact on bipolar disorders, psychotic disorders, and acute stress disorder remains unexplored. As an add-on intervention psychotherapy technique with beneficial outcome on psychophysiological functioning, AT represents a promising avenue towards expanding research findings of brain-body links beyond the current limits of the prevention and clinical management of number of mental disorders.

Bipolar disorder and type 2 diabetes mellitus: A bidirectional relationship

Background and objectivesOver the past few decades, research has revealed complex interactions between type 2 diabetes mellitus (T2DM) and a wide range of comorbid conditions. The present paper sought to examine the relationship between bipolar disorder and T2DM and clarify the clinical impact of therapeutic interventions, highlighting the interpretation and implications of recent literature reports.MethodsThe PubMed electronic database was searched for keywords “bipolar disorder” AND “diabetes” OR “glucose”. Based on this literature search, 15 meta-analyses/systematic reviews and numerous research studies were identified that examined interrelationships between bipolar disorders and T2DM.ResultsPatients with bipolar disorder have higher rates of T2DM compared to the general population. Further, type 2 diabetic patients with comorbid bipolar disorder often experience deteriorated long-term glucose control and increased cardiovascular morbidity and mortality. Recent literature suggests shared risk factors and underlying disease mechanisms. In addition, genetic factors, sedentary life-style, lack of exercise, increased simple carbohydrate intake, adverse effects of bipolar pharmacotherapy, and bipolar depressive symptoms phenomenology may affect glucose metabolism.ConclusionsThe observed bidirectional interaction merits screening for psychiatric disorders in T2DM and vice versa to allow for early detection and treatment of this at risk population. Selection of drugs with neutral metabolic effects and dose individualization hold significant promise for optimizing therapy with antipsychotic and antidiabetic agents. (AU)

Glycaemic Variability and Risk Factors of Pregnant Women with and without Gestational Diabetes Mellitus Measured by Continuous Glucose Monitoring.

Background: The aim of the study was to compare the continuous glucose monitoring (CGM)-determined glycaemic variability (GV) of pregnant women with gestational diabetes mellitus (GDM) and without GDM (CG; control group). The secondary aim was to evaluate the association between risk factors of diabetes in pregnancy and parameters of glyceamic control. Methods: Demographic, biometric and biochemical parameters were obtained for pregnant women (20-38 years old) who after an oral glucose tolerance test were examined by 7-day continuous glucose monitoring using a iPro®2 Professional CGM. Results: The differences in GV between women with GDM and CG compared by total area under glucose curve (total AUC, (mmol·day/L) was statistically significant (p = 0.006). Other parameters of glycaemic control such as mean glucose, standard deviation, coefficient of variation, J-index, % time-above target range 7.8 mmol/L (%TAR), % time-in range 3.5-7.8 mmol/L (%TIR), time-below target range 3.5 mmol/L (%TBR), glycated haemoglobin were not significantly different in the study groups. Risk factors (a family history of diabetes, pre-pregnancy BMI, higher weight gain and age) correlated with parameters of glycaemic control. Conclusions: We found a significant difference in GV of women with and without GDM by total AUC determined from CGM. TIR metrics were close to significance. Our work points at an increased GV in relation to the risk factors of GDM. Pregnant women with risk factors have higher probability of severe GV with its consequences on maternal and fetal health state.

Roma Ethnicity and Sex-Specific Associations of Serum Uric Acid with Cardiometabolic and Hepatorenal Health Factors in Eastern Slovakian Population: The HepaMeta Study.

Background: Health characteristics associated with uric acid (UA) in the Roma minority remain less well known. The study sought to determine the ethnicity- and sex-specific associations of serum UA with health factors in Eastern Slovakian Roma and non-Roma populations. Methods: Data from the comparative cross-sectional HepaMeta study conducted in Slovakia in 2011 were used. The study enrolled 452 Roma subjects (35.2% men) and 403 non-Roma individuals (45.9% men) aged 18-55 years. Results: All study parameters differed between the sexes in both the Roma and non-Roma participants (p < 0.05). UA was related to sex with odds ratio for female sex 0.873, 95% CI 0.853-0.893 (p < 0.0001) per 10-unit increase of UA. Average level of UA ± standard deviation was lower in Roma than in non-Roma (226.54 ± 79.8 vs. 259.11 ± 84.53 umol/L; p < 0.0001). The Roma population presented with greater levels of high-sensitivity C-reactive protein (hsCRP) (3.07 ± 4 mg/L vs. 1.98 ± 2.83 mg/L; p < 0.0001) and ferritin in Roma males (403.78 ± 391.84 vs. 302.67 ± 236.26 mg/L; p < 0.0001). Conclusions: Serum UA is sex- and ethnicity specific. Elevated levels of hsCRP and ferritin particularly in Roma males can reflect low-grade systemic inflammation and thus serve as a marker of an increased cardiovascular risk.

The altered circadian pattern of basal insulin requirements - an early marker of autoimmune polyendocrine syndromes in type 1 diabetes mellitus.

OBJECTIVES: The purpose of the present paper is to propose and introduce novel biomarkers of autoimmune polyendocrine syndromes that are relevant to the early diagnosis and optimal medical management of the patients who already suffer from type 1 diabetes mellitus. METHODS: We hypothesize and demonstrate on a case study that various organ-specific autoimmune endocrinopathies can result in lowered basal insulin requirements, leading to unexplained hypoglycemia. RESULTS: It can be hypothesized that hypothyroidism in patients with type 1 diabetes mellitus may deteriorate glycemic control and can lead to an increased rate of hypoglycemia, particularly the overnight and morning hypoglycemia. Thus, the decreased requirements for particularly overnight basal insulin can be an early marker of the autoimmune polyendocrine syndrome-3 with subclinical autoimmune thyroiditis in immune-mediated type 1 diabetes mellitus. Further, it could be proposed that unexplained hypoglycemia during the late afternoon or evening could be an early marker of the autoimmune polyendocrine syndrome-2 with subclinical autoimmune Addison disease in immune-mediated type 1 diabetes mellitus. As a result, an altered circadian pattern of basal insulin requirements can occur, characterized by a decreased late afternoon basal insulin rate. CONCLUSIONS: After exclusion of other causes, the unexplained reoccurring hypoglycemia can be a remarkable feature of autoimmune polyendocrine syndromes in immune-mediated type 1 diabetes mellitus on intensive insulin replacement therapy.

Update on Sexual Dimorphism in Brain Structure-Function Interrelationships: A Literature Review.

A remarkable feature of the human brain is its sexual dimorphism. While it is well documented that the sexual dimorphism in brain structure and function exists, its clinical implications in healthy individuals as well as in those who suffer from various neuropsychiatric disorders remain to be further explored. The present paper aims to provide an overview of the remarkable features and the fundamental characteristics of the sexual dimorphism in brain performance along with clinical implications based on the review of the relevant meta-analyses published up-to-date. The primary aim is to highlight and discuss the synthesized results to advance human knowledge in the area of applied psychophysiology and support direct future interdisciplinary research efforts towards improvements in health and quality of life with regard to sexual dimorphism in brain structure-function interrelationships. The review also seeks to advance clinical management approaches to sexually dimorphic neurocognitive conditions. Better understanding of the areas implicated in sex-biased neuropsychiatric disorders can help to improve sex-specific referrals, diagnosis and proactive care management of the patients and achieving treat-to-target goals.

Factors Associated With Presenteeism at Work in Type 2 Diabetes Mellitus.

OBJECTIVE: Our study aimed to identify factors associated with decreased presenteeism in type 2 diabetes mellitus (T2DM). METHODS: Data were collected from 147 T2DM participants. Questionnaires were completed: Stanford Presenteeism Scale (SPS-6) assessing health status and employee productivity, Hospital Anxiety and Depression Scale (HADS) for mental health, SF-36 for quality of life, Problem Areas in Diabetes (PAID) to measure diabetes-related emotional distress, and Michigan Neuropathy Screening Instrument for diabetic neuropathy. RESULTS: PAID score was negatively related to the SPS-6 score (r = -0.527, P < 0.001). Both anxiety and depression were negatively correlated with SPS-6 (r = -0.377, P < 0.001 and r = -0.603, P < 0.001, respectively). Seven out of eight different categories of SF-36 were significantly associated with SPS-6 score. Neuropathy was negatively related to presenteeism (r = -0.228, P = 0.07). CONCLUSION: Factors related to decreased presenteeism in T2DM include diabetes-associated stress, poor mental health, poor quality of life, and a history of neuropathy.

Pulmonary Function and Sleep Breathing: Two New Targets for Type 2 Diabetes Care.

Population-based studies showing the negative impact of type 2 diabetes (T2D) on lung function are overviewed. Among the well-recognized pathophysiological mechanisms, the metabolic pathways related to insulin resistance (IR), low-grade chronic inflammation, leptin resistance, microvascular damage, and autonomic neuropathy are emphasized. Histopathological changes are exposed, and findings reported from experimental models are clearly differentiated from those described in humans. The accelerated decline in pulmonary function that appears in patients with cystic fibrosis (CF) with related abnormalities of glucose tolerance and diabetes is considered as an example to further investigate the relationship between T2D and the lung. Furthermore, a possible causal link between antihyperglycemic therapies and pulmonary function is examined. T2D similarly affects breathing during sleep, becoming an independent risk factor for higher rates of sleep apnea, leading to nocturnal hypoxemia and daytime sleepiness. Therefore, the impact of T2D on sleep breathing and its influence on sleep architecture is analyzed. Finally, the effect of improving some pathophysiological mechanisms, primarily IR and inflammation, as well as the optimization of blood glucose control on sleep breathing is evaluated. In summary, the lung should be considered by those providing care for people with diabetes and raise the central issue of whether the normalization of glucose levels can improve pulmonary function and ameliorate sleep-disordered breathing. Therefore, patients with T2D should be considered a vulnerable group for pulmonary dysfunction. However, further research aimed at elucidating how to screen for the lung impairment in the population with diabetes in a cost-effective manner is needed.

Investigating physiological glucose excursions before, during, and after Ramadan in adults without diabetes mellitus.

AIM: The study aimed to investigate physiological effects of Ramadan fasting on continuously monitored glucose levels in relation to Ramadan in young non-diabetic adults. METHODS: Continuous glucose monitoring was employed to measure interstitial glucose for several days 1-2weeks before Ramadan, in the middle of Ramadan, and 4-6weeks after Ramadan to assess glucose exposure and glucose variability. RESULTS: A total of 34,182 accurate glucose sensor readings and 438 capillary blood glucose values [mean absolute difference median (interquartile range) 8.5 (6.9-11.1)%] were obtained from 18 non-diabetic adults [13 females; aged 24 (21-27) years; baseline body mass index 23.9 (20.6-28.9) kg/m2]. The continuous glucose monitoring profiles showed an increase in the hyperglycemic (above 140mg/dL) area under the curve after Ramadan compared to both before (P=0.004) and during Ramadan (P=0.003), along with an increased glucose variability after Ramadan (P=0.014). Both the area under the interstitial glucose concentration curve for the entire day and the average glucose were positively associated with body mass index during (P=0.004 and P=0.005, respectively) and after Ramadan (P=0.013 and P=0.01, respectively). Atypical continuous glucose patterns were recognized in 11% of subjects, distinguished by a prolonged increased glucose exposure, particularly in response to a meal. CONCLUSION: The time-point 4-6weeks after Ramadan was distinguished by greater glucose exposure and wider glucose variability that may reflect ongoing changes in insulin sensitivity in response to altering lifestyle patterns in non-diabetic young adults across the spectrum of body weight.

Is there a difference in progression of renal disease between South Asian and white European diabetic adults with moderately reduced kidney function?

AIMS: We examined potential ethnicity-related differences in progression of chronic kidney disease (CKD) between South Asian and white European diabetic adults with CKD stage 3 over a 5-year period. METHODS: We analysed data collected from diabetic adults of white European and South Asian ethnicity who had attended diabetes and diabetes-renal outpatient clinics with baseline estimated glomerular filtration rate (eGFR) values ≥30 and <60 ml/min/1.73 m(2) over 5 years (2005-2010); 891 (76%) were white Europeans, 282 (24%) were South Asians. RESULTS: Despite similar baseline eGFR (P=0.103), South Asians were younger [median (interquartile range) 68 (63-73) vs. 70 (64-77) years; P<0.001] and had worse baseline glycated haemoglobin than white Europeans [8.0 (7.0-9.1) vs. 7.6 (6.8-8.7)%; P=0.004]. The 5-year follow-up eGFR and the decline in eGFR did not differ between the two groups. Thirty-five (12.4%) South Asians and 82 (9.2%) white Europeans progressed to stages 4-5 CKD (P=0.112). There was a trend towards higher follow-up glycated haemoglobin levels in South Asians (P=0.064). CONCLUSIONS: Despite worse glycaemic control, South Asian diabetic adults with CKD stage 3 did not show any difference in 5-year decline in eGFR compared with white Europeans. These data do not support ethnic differences in progression of CKD between the South Asian and white European patient populations.

Predicting non-diabetic renal disease in type 2 diabetic adults: The value of glycated hemoglobin.

AIMS: The indications for renal biopsy in type 2 diabetes mellitus (T2D) are not well established. We investigated the prevalence, spectrum, and predictors of biopsy-proven non-diabetic renal disease (NDRD) in T2D. METHODS: An observational, single-center, retrospective study of T2D adults who underwent renal biopsies (N = 51) over 10 years for nephrotic-range proteinuria, microscopic hematuria, or rapidly declining renal function. RESULTS: Thirty-five (68.6%) biopsies were diagnostic of NDRD, and 16 (31.4%) revealed isolated diabetic nephropathy. The most common NDRDs were interstitial nephritis (20%), progressive crescentic glomerulonephritis (14%), membranous nephropathy (11%), and focal segmental glomerulosclerosis (11%). The odds for NDRD declined by 97% in the presence of diabetic retinopathy (P < 0.001). The deterioration of HbA1c during the year before biopsy predicted NDRD even after adjusting for diabetic retinopathy (OR, 7.65; 95% CI, 1.36-123.04; P = 0.003). A model based on the interaction between the HbA1c values 12 months before biopsy and the absolute change in these values during the preceding year predicted NDRD with 73.7% sensitivity and 75% specificity (AUC, 0.77; 95% CI, 0.59-0.94). CONCLUSIONS: This study demonstrated a considerably high prevalence of NDRD in T2D adults undergoing renal biopsy. The absence of diabetic retinopathy, lower HbA1c values 12 months before biopsy and greater deterioration in HbA1c prior to biopsy predicted NDRD in T2D. Further studies are needed to validate the findings.

Novel insights into metabolic sequelae of obstructive sleep apnoea: a link between hypoxic stress and chronic diabetes complications.

An increasing body of evidence suggests that obstructive sleep apnoea (OSA) is independently associated with an increased risk of cardiovascular disease, glucose intolerance, and deteriorations in glycaemic control. Despite the knowledge of a multifactorial pathogenesis of long-term diabetes complications, there is a paucity of information on impact of comorbidities associated with chronic intermittent hypoxemia on development and progression of chronic diabetes complications. This review explores the clinical and scientific overlap of OSA and type 2 diabetes mellitus (T2DM) and its possible impact on the development and progression of diabetes macrovascular and microvascular complications. Multiple prospective observational cohort studies have demonstrated that OSA significantly increases the risk of cardiovascular disease independent of potential confounding risk factors. The current evidence further suggests that OSA with concurrent T2DM is associated with an increased risk of oxidative stress-induced damage of vulnerable endothelial and mesangial cells and peripheral nerves. Further studies are needed to validate the impact of OSA treatment on diabetes micro- and macrovascular complications. Since it is presently still unknown whether OSA treatment may provide a diabetes-modifying intervention that could delay or halt the progression of chronic diabetes complications, the emphasis is on early diagnosis and satisfactory treatment of both OSA and T2DM.

Reversal of functional disorders by aspiration, expiration, and cough reflexes and their voluntary counterparts.

Agonal gasping provoked by asphyxia can save ~15% of mammals even from untreated ventricular fibrillation (VF), but it fails to revive infants with sudden infant death syndrome (SIDS). Our systematic study of airway reflexes in cats and other animals indicated that in addition to cough, there are two distinct airway reflexes that may contribute to auto-resuscitation. Gasp- and sniff-like spasmodic inspirations (SIs) can be elicited by nasopharyngeal stimulation, strongly activating the brainstem generator for inspiration, which is also involved in the control of gasping. This "aspiration reflex" (AspR) is characterized by SI without subsequent active expiration and can be elicited during agonal gasping, caused by brainstem trans-sections in cats. Stimulation of the larynx can activate the generator for expiration to evoke the expiration reflex (ExpR), manifesting with prompt expiration without preceding inspiration. Stimulation of the oropharynx and lower airways provokes the cough reflex (CR) which results from activating of both generators. The powerful potential of the AspR resembling auto-resuscitation by gasping can influence the control mechanisms of vital functions, mediating reversal of various functional disorders. The AspR in cats interrupted hypoxic apnea, laryngo- and bronchospasm, apneusis and even transient asphyxic coma, and can normalize various hypo- and hyper-functional disorders. Introduction of a nasogastric catheter evoked similar SIs in premature infants and interrupted hiccough attacks in adults. Coughing on demand can prevent anaphylactic shock and resuscitate the pertinent subject. Sniff representing nasal inspiratory pressure and maximal inspiratory and expiratory pressures (MIP and MEP) are voluntary counterparts of airway reflexes, and are useful for diagnosis and therapy of various cardio-respiratory and neuromuscular disorders.