Hormonal influence on renal function with particular reference to diabetes mellitus

Chapter 1 outlines the epidemiology, the functional stages, the pathogenesis and therapeutic aspects of renal disease in patients with insulin-dependent diabetes mellitus (IDDM). Several aspects of the pathogenesis of diabetic nephropathy (DN) are more extensively overviewed in sections on the influence of norepinephrine (NE) and the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis on renal function. Both substances belong to hormonal systems that control renal haemodynamics in opposite ways: NE causes renal vasoconstriction, the GH-IGF-I-axis induces renal vasodilatation. Since the early stages of diabetic renal involvement are characterised by an imbalance in glomerular vasodilation and vasoconstriction, the possible role of these humoral systems in diabetic nephropathy (DN) is discussed. The role of 11B-hydroxysteriod dehydrogenase (11B-HSD) in protecting the mineralcorticoid receptor from activation by cortisol is briefly recapitulated in the context of abnormalities in sodium and volume homeostasis in IDDM.

Probing archaeal cell biology: exploring the use of dyes in the imaging of Sulfolobus cells

Archaea are key players in many critical ecological processes. In comparison to eukaryotes and bacteria, however, our understanding of both the cell biology and diversity of archaea remains limited. While archaea inhabit a wide range of environmental conditions, many species are extremophiles, surviving in extreme temperature, salt or pH conditions, making their cell biology hard to study. Recently, our understanding of archaeal cell biology has been advanced significantly by the advent of live cell imaging in extremis as well as the development of genetic tools to exogenously express fluorescent proteins in some mesophilic archaeal model systems, e.g., Haloferax volcanii. However, for most archaeal species, especially thermophilic species or emerging model systems without well characterized genetic tools, live cell imaging remains dependent on fluorescent chemical probes to label and track the dynamics of living cells. While a wide range of fluorescent stains and markers that label different components of the cell are available commercially, their use has usually been optimized for use in a small number of eukaryotic cell systems. Here we report the successes and failures of the application of membrane, DNA, S-layer and cytoplasm markers in live cell imaging of archaea, as well as the optimization of fixation and immunolabelling approaches. We have applied these markers to the thermoacidophilic archaeon Sulfolobus acidocaldarius, but expect some to work in other archaeal species. Furthermore, those procedures that failed in S. acidocaldarius may still prove useful for imaging archaea that grow at a more neutral pH and/or at a less extreme temperature

Older Age, Polypharmacy, and Low Systolic Blood Pressure Are Associated With More Hypotension-Related Adverse Events in Patients With Type 2 Diabetes Treated With Antihypertensives

Background and Aims: Low systolic blood pressure (SBP) levels while being treated with antihypertensives may cause hypotension-related adverse events (hrAEs), especially in the elderly, women, and frail patients. We aimed to assess the association between the occurrence of hrAEs and low SBP levels, age, sex, and polypharmacy among patients with type 2 diabetes (T2D) treated with antihypertensives.Methods: In this cohort study, we used the Groningen Initiative to ANalyse Type 2 diabetes Treatment (GIANTT) database which includes patients managed for T2D in primary care from the north of the Netherlands. Patients treated with ≥1 antihypertensive drug and ≥1 SBP measurement between 2012 and 2014 were included. The outcome was the presence of an hrAE, i.e. postural hypotension, dizziness, weakness/tiredness, and syncope in 90 days before or after the lowest recorded SBP level. Age (≥70 vs. <70 years), sex (women vs. men), polypharmacy (5–9 drugs or ≥10 drugs vs. <5 drugs), and SBP level (<130 or ≥130 mmHg) were included as determinants. Logistic regression analyses were conducted for age, sex and polypharmacy, including the SBP level and their interaction, adjusted for confounders. Odds ratios (OR) with 95% confidence intervals (CI) are presented.Results: We included 21,119 patients, 49% of which were ≥70 years old, 52% were women, 57% had polypharmacy, 61% had an SBP level <130 mmHg and 5.4% experienced an hrAE. Patients with an SBP level <130 mmHg had a significantly higher occurrence of hrAEs than patients with a higher SBP level (6.2 vs. 4.0%; ORs 1.41, 95%CI 1.14–1.75, 1.43, 95%CI 1.17–1.76 and 1.33, 95%CI 1.06–1.67 by age, sex, and polypharmacy, respectively). Older patients (OR 1.29, 95%CI 1.02–1.64) and patients with polypharmacy (OR 5–9 drugs 1.27, 95%CI 1.00–1.62; OR ≥10 drugs 2.37, 95% CI 1.67–3.37) were more likely to experience an hrAE. The association with sex and the interactions between the determinants and SBP level were not significant.Conclusion: Low SBP levels in patients with T2D treated with antihypertensives is associated with an increase in hrAEs. Older patients and those with polypharmacy are particularly at risk of hrAEs. Age, sex, and polypharmacy did not modify the risk of hrAEs associated with a low SBP level

Changes in blood pressure thresholds for initiating antihypertensive medication in patients with diabetes: a repeated cross-sectional study focusing on the impact of age and frailty

Objective To assess trends in systolic blood pressure (SBP) thresholds at initiation of antihypertensive treatment in patients with type 2 diabetes and the impact of age and frailty on these trends.Study design and setting A repeated cross-sectional cohort study (2007–2014) using the Groningen Initiative to Analyse Type 2 diabetes Treatment database was conducted. The influence of calendar year, age or frailty and the interaction between year and age or frailty on SBP thresholds were assessed using multilevel regression analyses adjusted for potential confounders.Results We included 4819 patients. The mean SBP at treatment initiation was 157 mm Hg in 2007, rising to 158 mm Hg in 2009 and decreasing to 151 mm Hg in 2014. This quadratic trend was significant (p<0.001). Older patients initiated treatment at higher SBP, but similar decreasing trends after 2009 were observed in all age groups. There were no significant differences in SBP thresholds between patients with different frailty groups. The association between year and SBP threshold was not influenced by age or frailty.Conclusion After an initial rise, the observed SBP thresholds decreased over time and were not influenced by age or frailty. This is in contrast with changed guideline recommendations towards more personalised treatment during the study period and illustrates that changing prescribing practice may take considerable time. Patient-specific algorithms and tools focusing on when and when not to initiate treatment could be helpful to support personalised diabetes care

Self-tracking of physical activity in people with type 2 diabetes:a randomized controlled trial

The purpose of this study was to determine the efficacy of an online self-tracking program on physical activity, glycated hemoglobin, and other health measures in patients with type 2 diabetes. Seventy-two patients with type 2 diabetes were randomly assigned to an intervention or control group. All participants received usual care. The intervention group received an activity tracker (Fitbit Zip) connected to an online lifestyle program. Physical activity was analyzed in average steps per day from week 0 until 12. Health outcome measurements occurred in both groups at baseline and after 13 weeks. Results indicated that the intervention group significantly increased physical activity with 1.5 +/- 3 days per week of engagement in 30 minutes of moderate-vigorous physical activity versus no increase in the control group (P = .047). Intervention participants increased activity with 1255 +/- 1500 steps per day compared to their baseline (P <.010). No significant differences were found in glycated hemoglobin A1c, with the intervention group decreasing -0.28% +/- 1.03% and the control group showing -0.0% +/- 0.69% (P = .206). Responders (56%, increasing minimally 1000 steps/d) had significantly decreased glycated hemoglobin compared with nonresponders (-0.69% +/- 1.18% vs 0.22% +/- 0.47%, respectively; P = .007). To improve effectiveness of eHealth programs, additional strategies are needed

Insulinoma Manifesting Early Postpartum:Case Report and Review of the Literature

Objective: Insulinomas are insulin-producing neuroendocrine tumors. Insulinomas presenting during pregnancy and the early postpartum period are very rare. Methods: A 33-year-old woman with hypoglycemia early postpartum is described. Abdominal computed tomography and endoscopic ultrasound showed 2 lesions of the pancreas. An 11C-5-hydroxy-L-tryptophan (11CHTP) positron emission tomography-computed tomography (PET-CT) scan demonstrated additional uptake in lymph nodes and liver, suggesting malignant insulinoma. Six months after pylorus-preserving pancreatoduodenectomy and excision of liver and lymph node metastases, tumor progression was noted on repeated 11C-HTP PET-CT scans without recurrent hypoglycemia. She was enrolled in a clinical trial and was randomized for dual pan-class I phosphoinositide 3-kinase inhibitor and mammalian target of rapamycin inhibitor treatment, on which there was no tumor progression during 21 months follow-up. A systematic search of PubMed and Medline with the search strategy ‘insulinoma AND pregnancy’ OR ‘insulinoma AND postpartum’ was performed to identify English-, Dutch-, and German-language publications. All publications about (malignant) insulinoma during pregnancy and in the early postpartum period (≤3 months postpartum) were reviewed in addition to the described case report. Results: Insulinoma manifesting during pregnancy or early after delivery has been described in 31 cases, including only 3 cases of malignant insulinoma. Management of malignant insulinoma requires an individualized approach; optimal medical treatment is evolving. Conclusion: The usefulness of 11C-HTP PET-CT in the diagnosis of malignant insulinoma was demonstrated in the present case. Hypoglycemia may particularly become manifest in the postpartum period when insulin action increases consequent to decreased levels of placenta-derived counterregulatory hormones after delivery.</p

Sex Differences in Lipid Profile across the Life Span in Patients with Type 2 Diabetes:A Primary Care-Based Study

We assessed sex differences across the life span in the lipid profile of type 2 diabetes (T2D) patients treated and not treated with statins. We used the Groningen Initiative to ANalyze Type 2 diabetes Treatment database, which includes T2D patients from the north of the Netherlands. Patients with a full lipid profile determined between 2010 and 2012 were included. We excluded patients treated with other lipid-lowering drugs than statins. Sex differences in low- and high-density lipoprotein cholesterol (LDL-c and HDL-c) and triglyceride (TG) levels across 11 age groups stratified by statin treatment were assessed using linear regression. We included 26,849 patients (51% women, 55% treated with statins). Without statins, women had significantly lower LDL-c levels than men before the age of 45 years, similar levels between 45 and 49 years, and higher levels thereafter. With statins, similar LDL-c levels were shown up to the age of 55, and higher levels in women thereafter. Women had significantly higher HDL-c levels than men, regardless of age or statin treatment. Men had significantly higher TG levels up to the age of 55 and 60, depending on whether they did not take or took statins, respectively, and similar levels thereafter. When managing cardiovascular risk in patients with T2D, attention is needed for the menopausal status of women and for TG levels in younger men