Chronic diseases, such as type 2 diabetes (T2D), are difficult to manage because they demand continuous therapeutic review and monitoring. Beyond achieving the target HbA1c, new guidelines for the ...therapy of T2D have been introduced with the new groups of antidiabetics, glucagon-like peptide-1 receptor agonists (GLP-1ra) and sodium-glucose cotransporter-2 inhibitors (SGLT2-in). Despite new guidelines, clinical inertia, which can be caused by physicians, patients or the healthcare system, results in T2D not being effectively managed. This opinion paper explores the shift in T2D treatment, challenging assumptions and evidence-based recommendations, particularly for family physicians, considering the patient's overall situation in decision-making. We looked for the possible reasons for clinical inertia and the poor application of guidelines in the management of T2D. Guidelines for antidiabetic drugs should be more precise, providing case studies and clinical examples to define clinical contexts and contraindications. Knowledge communication can improve confidence and should include clear statements on areas of decision-making not supported by evidence. Precision medicine initiatives in diabetes aim to identify subcategories of T2D patients (including frail patients) using clustering techniques from data science applications, focusing on CV and poor treatment outcomes. Clear, unconditional recommendations for personalized T2D management may encourage drug prescription, especially for family physicians dealing with diverse patient contexts and clinical settings.
Introduction: Diabetic foot ulceration (DFU) is associated with high morbidity, mortality, and represents the
leading cause of hospitalization in patients with diabetes. Peripheral arterial disease ...(PAD), present in half
of patients with DFU, is an independent predictor of lower limb amputation (LLA) and can be difficult to
diagnose in a diabetic population. Underdiagnosis and undertreatment of critical PAD are frequent.1-3 To our
knowledge there is no data about LLA incidence in Croatia neither in diabetics nor in nondiabetics. Our aim
was to determine the incidence of amputation in patients with diabetes mellitus in Osijek-Baranja County.
Patients and Methods: This was a tertiary-care-based retrospective study involving adult patients in
whom amputation were performed for reasons relating to complication of PAD and/or diabetes in the
University Hospital Centre Osijek from 1st January 2008 to 31st December 2018. We calculated LLA rates
using estimates of the population with diabetes derived from CroDiab registry and Croatian Institute
for Public Health for Osijek-Baranja County. LLAs were further categorized by level of amputation as
follows: minor (toe and foot) and major (above foot and below knee, and above knee).
Results: There were 1551 LLAs in ten-year period. Smaller proportion of amputation was above foot
(49.3% vs 59.3%). LLA rates per 1,000 adults with diabetes decreased 29% between 2010 and 2013 and
then increased 76 % between 2014 and 2018 (Figure 1). We observed the same pattern in both minor and
major LLA but rates of amputation above knee steadily increased 2.65 times between 2010 and 2018
(from 0.69 to 1.83 LLA per 1,000 patients).
Conclusion: This study confirmed high rate of lower limb amputation in diabetic patients in Osijek-
Baranja County which is representative for east Croatia region. After a decline of low limb amputations in
diabetic patients between 2011 and 2013, LLA rates began to increase from 2014 to 2018. Reasons for that
reversal trend are unclear. It can be due to poor management of CVD risk factors, poor glycemic control,
and failure in early detection of PAD. It is also possible that change in health policy and organization of
diabetes care together with socioeconomic factors could affect trends of LLA. Incidence rate of LLA in
our population is important for further improvements in diabetes care and for decisions in health policy.
Antidiuretic hormone (ADH) is secreted by the posterior pituitary gland. Unsuppressed release of ADH leads to hyponatremia. This condition is referred to as syndrome of inappropriate antidiuretic ...hormone secretion (SIADH). Hereby, a case report is presented on ciprofloxacin-induced SIADH. A 67-year-old male patient was examined in the emergency room with symptoms of lethargy, headache, lack of attention, and a generally depressed mood lasting for three days. One week prior, empirical antimicrobial therapy involving ciprofloxacin for prostatitis was initiated. Laboratory analysis showed no relevant abnormalities except for hyponatremia (Na = 129 mmol/L). Chronic hyponatremia, thyroid dysfunction, and adrenal dysfunction were ruled out. Serum osmolality was 263 mOsmol/kg, urine osmolality was 206 mOsmol/kg, and urine sodium was 39 mmol/L. Given that all criteria for SIADH were met, ciprofloxacin was discontinued, and fluid restriction was advised. Four days later, the patient's serum sodium concentrations nearly normalized (Na = 135 mmol/L), and all symptoms resolved. The Naranjo Scale yielded a score of 8, supporting the likelihood of a probable adverse reaction to ciprofloxacin. This case is presented to raise awareness among clinicians about the potential of ciprofloxacin to cause even mild hyponatremia.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class of drugs that have primarily been used in the treatment of type 2 diabetes. However, as new findings from clinical trials have ...become available, their indication has been expanded to include treatment of heart failure and chronic kidney disease without the presence of diabetes. The pathophysiological mechanisms of extraglycemic effects of SGLT2i are still being unraveled, but one of the most prominent consequences is a decrease in blood pressure, which has implications for hemodynamics and arterial stiffness. Recent findings indicate that this class of drugs has a beneficial effect on lowering nocturnal blood pressure (BP), with special importance in type 2 diabetes (DMT2), since unregulated nocturnal hypertension is associated with an increased incidence of cardiovascular (CV) events. In this mini-review, we have summarized current knowledge about the effects of SGLT2i on blood pressure, including office, home, and ambulatory BP, and potential implications for treatment of hypertension in diabetic and non-diabetic individuals, with positive effects on cardiorenal outcomes.
Pravilna prehrana iznimno je važna u prevenciji šećerne bolesti i regulaciji glikemije. Šećerna bolest ubraja se u kategoriju bolesti koje se uspješno mogu prevenirati, dobro liječiti te im se može ...spriječiti ili odgoditi razvoj kroničnih komplikacija. Edukacija o pravilnoj prehrani treba biti individualno prilagođena, pri čemu treba obratiti pozornost na dob bolesnika, način života, socioekonomski status, tjelesnu aktivnost i komplikacije vezane uz šećernu bolest. Kod šećerne bolesti promjena životnih navika, što uključuje pravilnu prehranu, redovitu tjelesnu aktivnost i regulaciju tjelesne mase, može uvelike pridonijeti regulaciji glikemije, a u tipu 2 u nekim slučajevima može dovesti i do njene remisije. Smjernice su rezultat suradnje zdravstvenih stručnjaka koji sudjeluju u liječenju i edukaciji osoba koje boluju od šećerne bolesti. Utemeljene su na dokazima, prema metodologiji GRADE (engl. grading of recommendations, assessment, development and evaluation) koja uz snagu dokaza opisuje i razinu preporuke. Temeljni zaključci ovih smjernica odnose se na procjenu nutritivnih potreba te primjenu medicinske nutritivne terapije, individualno prilagođene osobama sa šećernom bolešću kao i onima koji imaju i neke od
vezanih komorbiditeta.
Chronic exposure to high inorganic As levels in drinking water has been related to many diseases, including type 2 diabetes mellitus (T2D). The association with low and moderate As levels, however, ...remains controversial and has yet not been studied in European populations.
This study aimed to investigate possible association between As exposure and biomarkers of T2D in Croatian population. Observation recruited 86 adults from Eastern Croatia, where groundwater is contaminated with inorganic As, and 116 adults from Western Croatia, where As levels in drinking water are low. Both populations were divided in patient groups (T2D or prediabetes) and healthy controls. Exposure was assessed by determining total As in blood and urine and As metabolites in urine.
Eastern Croatian population had a significantly higher content of As in urine than Western, whereas the opposite was true for arsenobetain. Total As and As metabolites in urine positively correlated with hemoglobin A1c (HbA1c) and negatively with albuminuria.
This study provides important preliminary data on the levels of As in urine and blood and their association with biomarkers of T2D in Croatian population exposed to low or moderate levels of As through drinking water as a solid basis for further research of the pathophysiological effects of such As exposure on the status and complications of diabetes.
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•This is first study providing data on urinary levels of As species in Croatian population.•Correlation between As in urine and blood with biomarkers of diabetes were investigated.•Higher concentrations of As species in urine were associated with geographical origin.•As levels in urine positively correlated with HbA1c and negatively with albuminuria
Women with type 2 diabetes mellitus (T2DM) have a higher risk of fractures despite increased bone mineral density (BMD). In experimental studies a potential role of plasminogen activator inhibitor-1 ...(PAI-1) in bone remodeling is suggested but studies in humans are lacking. This is a first study in humans investigating whether circulated levels of PAI-1 in postmenopausal women with T2DM are related to BMD and adiposity.
Anthropometric variables, PAI-1 and insulin levels, serum lipids and bone turnover markers were measured in 127 postmenopausal women with T2DM. A total of 117 female patients were divided according to lumbar spine BMD measurements via dual-energy x-ray absorptiometry in three groups: 47 with osteopenia, 21 with osteoporosis and 49 with normal BMD.
Diabetic patients with normal BMD had significantly higher BMI, greater waist circumference and lower bone turnover markers than diabetics with osteopenia and osteoporosis. PAI-1 was lower in diabetics with osteoporosis and osteopenia compared with diabetics with normal BMD. Multiple regression analysis revealed insulin, triglycerides levels, pyrilinks and beta blocker therapy to be the strongest predictors of PAI-1 levels. PAI-1 levels correlated with both L-BMD and hip BMD, but after adjustment for age and BMI association was no longer significant.
Our findings suggest that elevated PAI-1 levels are associated with higher BMD in obese diabetic patients but the possible implications of this finding and underlying mechanisms still remain unclear. Obviously, metabolic parameters, may affect both BMD and PAI-levels, and association of PAI-1 and BMD could be indirect. However, as pyrilinks is also independently and significantly negatively correlated to PAI-1 its direct involvement in bone metabolism is also plausible. Further investigations are needed to elucidate the nature of interaction of this matrix modulator in relation to energy and bone metabolism in humans.
Interleukin (IL)-10 is an anti-inflammatory cytokine, and a decrease in its secretion is associated with obesity, metabolic syndrome and type 2 diabetes. However, it has not been established whether ...the intensity of the immune response during diabetes-associated chronic inflammation affects the development and/or progression of type 2 diabetes and its microvascular complications. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP)-1082G/A for IL-10 gene in development of diabetes type 2 and its complications. DNA was extracted from blood cells of 240 overweight/obese subjects for IL-10 genotyping. Based on the presence of diabetes type 2, patients were divided in two groups: experimental group of 144 patients with diabetes type 2 and control group of 96 age- and gender-matched subjects without diabetes. Compared to control group, diabetic group had higher levels of leukocytes (p=0.012), fibrinogen (p=0.049) and plasminogen activator inhibitor-1 (PAI-1) (p=0.009), and lower levels of albumin (p=0.001). There were no differences in the frequency of SNP-1082G/A for IL-10 gene between the two groups (p=0.654). When considering diabetes related traits in all subjects in relation to specific genotype, a group with homozygous (AA) genotype had higher values of the mean fasting glucose (p<0.000001), HbA1c (p<0.000001) and HOMA-IR (p=0.003632), while the mean HOMA-B value (p=0.000178) was lower when compared to the groups with GG and GA genotypes. There was no difference in devel-opment of diabetic nephropathy, retinopathy and polyneuropathy between the IL-10 polymorphism genotypes. In conclusion, obese diabetes type 2 patients had an increased inflammation activity com-pared to obese non-diabetic individuals. There was no association of the investigated polymorphisms and development of type 2 diabetes and its microvascular complications. However, diabetes related traits clearly depended on the presence of specific IL-10 genotype.
Summary
Objective
Connection between abdominal obesity, type 2 diabetes, and the hypothalamic-pituitary-adrenal (HPA) axis activity remains unclear. The aim of this study was to measure HPA axis ...activity in 121 type 2 diabetics, in 29 obese subjects, and 19 control subjects.
Research design and methods
Physical examination, anthropometric measures, psychological questionnaire, psychiatric interview, neurological and ophthalmologic examination were performed. Biochemical parameters, urinary free cortisol levels (UFC), cortisol and ACTH levels at 8 and 16 h, cortisol levels after overnight suppression with 1 mg dexamethasone followed by ACTH test in 30 and 60 min were measured. Groups were stratified in relation to obesity, body fat distribution, and chronic complications.
Results
UFC and postdexamethasone cortisol were significantly increased in diabetic patients compared with both obese subjects (
p
< 0.01) and control group (
p
< 0.05), regardless to diabetic complications and obesity. Postdexamethasone cortisol was correlated with waist circumference. ACTH-induced cortisol levels were significantly higher in all type 2 diabetic patients. An independent association was found between AUC cortisol in ACTH test and insulin resistance. Multiple regression analysis showed that waist circumference was independently associated with sex, fasting plasma insulin, morning cortisol, and AUC of cortisol in ACTH test (
R
2
= 0.334,
p
< 0.0000).
Conclusions
In type 2 diabetic patients, the HPA axis is clearly hyperactive as evident in increased urinary free cortisol, diminished cortisol suppression after dexamethasone and increased ACTH-induced cortisol levels. Abdominal obesity and the presence of chronic complications increased the HPA axis hyperactivity in type 2 diabetes. Augmentation of positive feedback is associated with insulin resistance and negative feedback with abdominal obesity.
Radna skupina Hrvatskog društva za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora pripremila je smjernice za postupanje u pandemiji COVID-19 za osobe sa šećernom bolešću i za ...zdravstvene
djelatnike. U preporukama su naglašeni razmjeri pandemije i moguće posljedice za oboljele od šećerne bolesti. Opisana je klinička slika i ponovljene smjernice Nacionalnog stožera civilne zaštite kako se osobe od šećerne bolesti mogu zaštititi i što trebaju činiti za dobru regulaciju glikemije. Predložene su mjere koje trebaju provoditi zdravstvene
ustanove koje skrbe o bolesnicima sa šećernom bolešću i načela zbrinjavanja glikemije u hitnom prijemu i tijekom hospitalizacije.
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