Implementation of a clinical decision support system for the optimization of antidiabetic drug orders by pharmacists.

AIMS: The objective of the study was to describe the impact of a clinical decision support system (CDSS) on antidiabetic drug management by clinical pharmacists for hospitalized patients with T2DM. METHODS: We performed a retrospective, single-centre study in a teaching hospital, where clinical pharmacists analysed prescriptions and issued pharmacist interventions (PIs) through a computerized physician order entry (CPOE) system. A CDSS was integrated into the pharmacists' workflow in July 2019. We analysed PIs during 2 periods of interest: one before the introduction of the CDSS (from November 2018 to April 2019, PIs issued through the CPOE alone) and one afterwards (from November 2020 to April 2021, PIs issued through the CPOE and/or the CDSS). The study covered nondiabetology wards as endocrinology, diabetes and metabolism departments were not computerized at the time of the study. RESULTS: There were 203 PIs related to antidiabetic drugs in period 1 and 319 in period 2 (a 57.5% increase). Sixty-four of the 319 PIs were generated by the CDSS. Noncompliance/contraindication was the main problem identified by the CDSS (41 PIs, 68.4%), and 57.8% led to discontinuation of the drug. Most of the PIs issued through the CDSS corresponded to orders that had not been flagged up by clinical pharmacists using the CPOE. Conversely, most alerts about indications that were not being treated were detected by the clinical pharmacists using the CPOE and not by the CDSS. CONCLUSION: Use of CDSS by clinical pharmacists improved antidiabetic drug management for hospitalized patients with T2DM. The CDSS might add value to diabetes care in nondiabetology wards by decreasing the frequency of potentially inappropriate prescriptions and adverse drug reactions.

Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study.

Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.

Risk factors for the development or progression of diabetic retinopathy in pregnancy: Meta-analysis and systematic review.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population, and it increases in severity during pregnancy. METHODS: Systematic review of literature from PubMed, Cochrane Library and Web of Science using keywords 'diabetic retinopathy' and 'pregnancy' and 'progression' from inception to 2021 was completed. Included studies were (1) peer-reviewed observational studies addressing progression/development of DR in pregnancy, (2) provided the number of diabetic patients that developed/progressed in DR during pregnancy, and (3) included differential data on variables between progression and non-progression groups. This was applied by two independent researchers and referred to a third researcher as necessary. Twenty-seven of the original 138 studies met this criterion. Data were pooled and analysed using fixed-effects in meta-analysis. RESULTS: From 27 studies, 2537 patients were included. Pre-eclampsia [Risk Ratio (RR) 2.62 (95% CI = 1.72, 4.00)] and hypertension treatment during pregnancy [RR 2.74 (95% CI = 1.72, 4.00)] were significantly associated with the development/progression of DR. HbA1c at baseline [MD 0.82 (95% CI = 0.59, 1.06)], duration of diabetes [mean difference (MD) 5.97 (95% CI = 5.38, 6.57)], and diastolic blood pressure at baseline [MD 3.29 (95% CI = 0.46, 6.12)] were all significantly higher in the progression group while only mean birth weight [MD -0.17 (95% CI = -0.31, -0.03)] was significantly higher in the non-progression group. CONCLUSIONS: This study fills a gap in the literature and provide physicians with more information on the risk factors associated with the progression of DR in pregnancy and how to counsel this vulnerable patient population appropriately.

A systematic review of the value of clinical decision support systems in the prescription of antidiabetic drugs.

INTRODUCTION: The management of chronic diabetes mellitus and its complications demands customized glycaemia control strategies. Polypharmacy is prevalent among people with diabetes and comorbidities, which increases the risk of adverse drug reactions. Clinical decision support systems (CDSSs) may constitute an innovative solution to these problems. The aim of our study was to conduct a systematic review assessing the value of CDSSs for the management of antidiabetic drugs (AD). MATERIALS AND METHODS: We systematically searched the scientific literature published between January 2010 and October 2023. The retrieved studies were categorized as non-specific or AD-specific. The studies' quality was assessed using the Mixed Methods Appraisal Tool. The review's results were reported in accordance with the PRISMA guidelines. RESULTS: Twenty studies met our inclusion criteria. The majority of AD-specific studies were conducted more recently (2020-2023) compared to non-specific studies (2010-2015). This trend hints at growing interest in more specialized CDSSs tailored for prescriptions of ADs. The nine AD-specific studies focused on metformin and insulin and demonstrated positive impacts of the CDSSs on different outcomes, including the reduction in the proportion of inappropriate prescriptions of ADs and in hypoglycaemia events. The 11 nonspecific studies showed similar trends for metformin and insulin prescriptions, although the CDSSs' impacts were not significant. There was a predominance of metformin and insulin in the studied CDSSs and a lack of studies on ADs such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. CONCLUSION: The limited number of studies, especially randomized clinical trials, interested in evaluating the application of CDSS in the management of ADs underscores the need for further investigations. Our findings suggest the potential benefit of applying CDSSs to the prescription of ADs particularly in primary care settings and when targeting clinical pharmacists. Finally, establishing core outcome sets is crucial for ensuring consistent and standardized evaluation of these CDSSs.

Lipomatoses.

Lipomatoses are benign proliferation of adipose tissue. Lipomas (benign fat tumors) are the most common component of lipomatosis. They may be unique or multiple, encapsulated or not, subcutaneous or sometimes visceral. In some cases, they form large areas of non-encapsulated fat hypertrophy, with a variable degree of fibrosis. They can develop despite the absence of obesity. They may be familial or acquired. At difference with lipodystrophy syndromes, they are not associated with lipoatrophy areas, except in some rare cases such as type 2 familial partial lipodystrophy syndromes (FPLD2). Their metabolic impact is variable in part depending on associated obesity. They may have functional or aesthetic consequences. Lipomatosis may be isolated, be part of a syndrome, or may be visceral. Isolated lipomatoses include multiple symmetrical lipomatosis (Madelung disease or Launois-Bensaude syndrome), familial multiple lipomatosis, the painful Dercum's disease also called Adiposis Dolorosa or Ander syndrome, mesosomatic lipomatosis also called Roch-Leri lipomatosis, familial angiolipomatosis, lipedema and hibernomas. Syndromic lipomatoses include PIK3CA-related disorders, Cowden/PTEN hamartomas-tumor syndrome, some lipodystrophy syndromes, and mitochondrial diseases, especially MERRF, multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson disease, Pai or Haberland syndromes. Finally, visceral lipomatoses have been reported in numerous organs and sites: pancreatic, adrenal, abdominal, epidural, mediastinal, epicardial… The aim of this review is to present the main types of lipomatosis and their physiopathological component, when it is known.

Development of explicit definitions of potentially inappropriate prescriptions for antidiabetic drugs in patients with type 2 diabetes: A multidisciplinary qualitative study.

PURPOSE: The management of type 2 diabetes mellitus patients has changed over the past decade, and a large number of antidiabetic drug treatment options are now available. This complexity poses challenges for healthcare professionals and may result in potentially inappropriate prescriptions of antidiabetic drugs in patients with type 2 diabetes mellitus which can be limited using screening tools. The effectiveness of explicit tools such as lists of potentially inappropriate prescriptions has been widely demonstrated. The aim was to set up nominal groups of healthcare professionals from several disciplines and develop a list of explicit definition of potentially inappropriate prescriptions of antidiabetic drugs. METHODS: In a qualitative, nominal-groups approach, 30 diabetologists, general practitioners, and pharmacists in France developed explicit definitions of potentially inappropriate prescriptions of antidiabetic drugs in patients with type 2 diabetes mellitus. A nominal group technique is a structured method that encourages all the participants to contribute and makes it easier to reach an agreement quickly. Each meeting lasted for two hours. RESULTS: The three nominal groups comprised 14 pharmacists, 10 diabetologists, and 6 general practitioners and generated 89 explicit definitions. These definitions were subsequently merged and validated by the steering committee and nominal group participants, resulting in 38 validated explicit definitions of potentially inappropriate prescriptions of antidiabetic drugs. The definitions encompassed four contexts: (i) the temporary discontinuation of a medication during acute illness (n = 9; 24%), (ii) dose level adjustments (n = 23; 60%), (iii) inappropriate treatment initiation (n = 3; 8%), and (iv) the need for further monitoring in the management of type 2 diabetes mellitus (n = 3; 8%). CONCLUSION: The results of our qualitative study show that it is possible to develop a specific list of explicit definitions of potentially inappropriate prescriptions of antidiabetic drugs in patients with type 2 diabetes mellitus by gathering the opinions of healthcare professionals caring for these patients. This list of 38 explicit definitions necessitates additional confirmation by expert consensus before use in clinical practice.

Polycystic ovary syndrome and adipose tissue.

Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women of reproductive age. Typically, it is associated with ovulatory dysfunction: dysovulation or anovulation, and symptoms of hyperandrogenism. It incurs risk of metabolic disorders such as diabetes, dyslipidemia and fatty liver. As a key endocrine organ in metabolic homeostasis, adipose tissue is often implicated in these complications. Studies of white adipose tissue (WAT) in PCOS have focused on the mechanism of insulin resistance in this tissue. Clinically, abnormalities in WAT distribution are seen, with decreased waist-to-hip ratio and increased ratio of adipose to lean mass. Such abnormalities are greater when total circulating androgens are elevated. At tissue level, white adipocyte hyperplasia occurs, along with infiltration of macrophages. Secretion of adipokines, cytokines and chemo-attractant proteins is increased in a pro-inflammatory manner, leading to reduced insulin sensitivity via alteration of glucose transporters, and hence decreased glucose uptake. The kinetics of non-esterified fatty acids (or free fatty acids) is also altered, leading to lipotoxicity. In recent years, brown adipose tissue (BAT) has been studied in women with PCOS. Although abundance is low in the body, BAT appears to play a significant role in energy expenditure and metabolic parameters. Both supra-clavicular skin temperature, which reflects BAT activity, and BAT mass are reduced in women with PCOS. Moreover, BAT mass and body mass index (BMI) are inversely correlated in patients. In the adipocyte, increased total circulating androgen levels reduce expression of uncoupling protein 1 (UCP1), a key protein in the brown adipocyte, leading to reduced biogenesis and mitochondrial respiration and hence a reduction in post-prandial thermogenesis. BAT is currently being investigated as a possible new therapeutic application.

Description of a French Population of Diabetics Treated Followed up by General Practitioners.

In France, the prevalence of treated diabetes has been estimated at 4.6%, or more than 3 million people and 5.2% in Northern France. The reuse of primary care data allows to study outpatient clinical data such as laboratory results and drug prescriptions, which are not documented in claims and hospital databases. In this study, we selected the population of treated diabetics from the Wattrelos primary care data warehouse, in North of France. Firstly, we studied the laboratory results of diabetics by identifying whether the recommendations of the French National Authority for Health (HAS) were respected. In a second step, we studied the prescriptions of diabetics by identifying the oral hypoglycemic agents treatments and insulins treatments. The diabetic population represents 690 patients of the health care center. The recommendations on labortatory are respected for 84% of diabetics. The majority of diabetics are treated with oral hypoglycemic agents 68.6%. As recommended by the HAS, metformin is the first-line treatment in the diabetic population.

Inter-Professional Communications During Follow-Up of Type 2 Diabetes Patients: An Exploratory Study.

Follow-up of patients with type 2 diabetes mellitus (T2DM) involves several healthcare professionals. The quality of their communication is crucial for optimizing care. This exploratory work aims to characterize those communications and their problems. Interviews were performed with general practitioners (GP), patients and other professionals. Data were analyzed deductively, and results were structured through a people map. We performed 25 interviews. GP, patients, nurses, community pharmacists, medical specialists and diabetologists are the main actors of the T2DM patients' follow-up. Three communication issues were identified: difficulties in reaching the hospital diabetologist, delays in receiving reports, and difficulties for patient to transmit information. Results were discussed in terms of tools, care pathways and new roles to support communications during T2DM patients' follow-up.

Pre-gestational diabetes and the risk of congenital heart defects in the offspring: A French nationwide study.

AIM: To compare the frequencies and types of congenital heart defects for infants of women without and with pre-gestational diabetes, type 1 and type 2 diabetes (T1DM, T2DM) and to identify risk factors. METHODS: All live births between 2012 and 2020 were screened for maternal diabetes and infant congenital heart defects using the French Medical Information System Program in Medicine, Surgery and Obstetrics database (PMSI-MCO). Incidences of these defects were estimated, and a logistic model evaluated maternal and fetal prognostic risk factors. RESULTS: Overall, 6,038,703 mothers did not have pre-gestational diabetes (no-diabetes), 23,147 had T1DM, and 14,401 had T2DM. The incidence of infant congenital disease was 6.2% for the no-diabetes group, 8.0%, for women with T1DM, and 8.4% for women with T2DM (P < 0.001); for congenital heart defects, incidences were respectively 0.8%, 3.0% and 2.7% (P < 0.001). In comparison with the no-diabetes group, the odds ratios (95%CI) of coronary heart defects were 2.07 (1.91;2.24) (P < 0.001) for women with T1DM and 2.20 (1.99;2.44) (P < 0.001) for women with T2DM, with no difference between T1DM and T2DM (P = 0.336). cesarian section, small and large for gestational age, and prematurity were also associated with an increased risk of congenital heart defects. CONCLUSION: In this study we observed higher incidences of congenital heart defects in infants of women with pre-gestational diabetes compared to women without pre-gestational diabetes, with no difference between women with T1DM or T2DM. These data call for intensifying preconception care and justify systematic cardiac echography in selected fetuses.

Cognitive Outcome After Islet Transplantation.

Severe or repeated hypoglycemia events may favor memory complaints in type 1 diabetes (T1D). Pancreatic islet transplantation (IT) is an alternative option to exogenous insulin therapy in case of labile T1D, implying a maintenance immunosuppression regimen based on sirolimus or mycophenolate, associated with tacrolimus, that may also have neurological toxicity. The objective of this study was to compare a cognitive rating scale Mini-Mental State Examination (MMSE) between T1D patients with or without IT and to identify parameters influencing MMSE. Methods: This retrospective cross-sectional study compared MMSE and cognitive function tests between islet-transplanted T1D patients and nontransplanted T1D controls who were transplant candidates. Patients were excluded if they refused. Results: Forty-three T1D patients were included: 9 T1D patients before IT and 34 islet-transplanted patients (14 treated with mycophenolate and 20 treated with sirolimus). Neither MMSE score (P = 0.70) nor higher cognitive function differed between islet versus non-islet-transplanted patients, whatever the type of immunosuppression. In the whole population (N = 43), MMSE score was negatively correlated to glycated hemoglobin (r = -0.30; P = 0.048) and the time spent in hypoglycemia on the continuous glucose monitoring (r = -0.32; P = 0.041). MMSE score was not correlated to fasting C-peptide level, time spent in hyperglycemia, average blood glucose, time under immunosuppression, duration of diabetes, or beta-score (success score of IT). Conclusions: This first study evaluating cognitive disorders in islet-transplanted T1D patients argues for the importance of glucose balance on cognitive function rather than of immunosuppressive treatment, with a favorable effect of glucose balance improvement on MMSE score after IT.

The heart, an endocrine gland: Natriuretic peptides.

The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). ANP and BNP, secreted by the heart, act as cardiac hormones, whereas CNP is an endothelial peptide. The aim of this manuscript is to review the production, action mechanisms, effects and clinical applications of natriuretic peptides.

Intermittently scanned continuous glucose monitoring is associated with lower spontaneous abortion rate compared with conventional blood glucose monitoring in pregnant women with type 1 diabetes: An observational study.

AIM: The objective of the present real-life study in France was to assess and compare characteristics and outcomes in a cohort of pregnant women with type 1 diabetes (T1D) using intermittently scanned continuous glucose monitoring (isCGM) or conventional blood glucose monitoring (BGM). MATERIAL AND METHODS: We performed an observational study of a cohort of 153 women with T1D: 77 women were using isCGM, and 76 were using BGM. We compared the groups' maternal characteristics and maternal-fetal complications. The level of HbA1c was measured before pregnancy and then four times (after 8-12, 24-28, 30-33, and 35-37 weeks of gestation). RESULTS: The two groups were similar in terms of age, prepregnancy BMI, diabetes duration, and diabetic vascular complications. There were no significant intergroup differences in the obstetric history. The spontaneous abortion rate was lower in the isCGM group than in the blood glucose monitoring group (5.3% vs. 20%, respectively; p = .0129), while the prepregnancy and first-trimester HbA1c levels were similar. There were no significant intergroup differences in the incidence of other maternal-fetal complications. CONCLUSIONS: This observational study demonstrates that isCGM use is associated with lower spontaneous abortion compared with conventional BGM. Large prospective studies are needed to corroborate our findings and fully understand the relationship between glucose data at the time of conception/early pregnancy and foetal outcome.

HbA1c at the time of testing for gestational diabetes identifies women at risk for pregnancy complications.

OBJECTIVE: It is unclear whether glycated haemoglobin (HbA1c) has utility in predicting adverse outcomes in gestational diabetes mellitus (GDM). The aims of the study were to examine the predictive value of HbA1c at GDM diagnosis with adverse pregnancy outcomes. RESEARCH DESIGN AND METHODS: This was a cohort study of 4,383 women with GDM between 2011 and 2018. We assessed the association of HbA1c with pregnancy outcomes using logistic regression models before and after adjustment for predefined risk factors of GDM. We examined these associations considering HbA1c as categorical variables using five pre-specified HbA1c classes: and as a continuous variable. RESULTS: An HbA1c ≥ 5.6% (38 mmol/mol) identified women with at greater risk for macrosomia: odds ratio (OR) [95% confidence interval] = 2.12 [1.29; 3.46] for HbA1c = 5.6-5.9% and 2.06 [1.14; 3.70] for HbA1c > 5.9% versus HbA1c ≤ 4.5% (26 mmol/mol). Similarly, HbA1c ≥ 5.6% (38 mmol/mol) was associated with greater risk for caesarean: 1.64 [1.06; 2.53] for HbA1c = 5.6-5.9% and 1.58 [0.93; 2.7] for HbA1c > 5.9% (41 mmol/mol) versus HbA1c ≤ 4.5% (26 mmol/mol). Using HbA1c ≤ 4.5% (26 mmol/mol) as reference category, HbA1c > 5.9% (41 mmol/mol) increased the OR of preterm delivery to 3.33 [1.27; 8.71]. HbA1c remained significant for Adverse Pregnancy Outcome Composite after adjustment (P < 0.0001). DISCUSSION: Our finding suggests that a single HbA1c reading may be a useful pragmatic tool to identify women at risk. Such identification may be a useful guide for identifying and applying preventative treatment for women at increased risk.

Association Between HbA1c Levels on Adverse Pregnancy Outcomes During Pregnancy in Patients With Type 1 Diabetes.

CONTEXT: Despite optimization of metabolic balance during pregnancy in type 1 diabetes (T1D), maternal-fetal complications remain higher than in the background population. OBJECTIVE: We examined whether there is an association between glycated hemoglobin (HbA1c) levels and these complications. METHODS: Retrospective study of pregnancies in 678 T1D subjects at Lille Hospital (1997-2019). The association between variations in HbA1c levels and complications was examined. The composite criterion (CC) was defined as having at least 1 of the following complications: prematurity, pre-eclampsia, large for gestational age (LGA), small for gestational age (SGA), or cesarean section. RESULTS: Among the 678 births, median preconception HbA1c was 7.2% (55 mmol/mol), 361 were LGA (56%), 29 were SGA (4.5%), and 504 were births without preterm delivery (76.1%). The CC occurred in 81.8%. Higher HbA1c during the first trimester was associated with the CC (OR 1.04; 95% CI 1.02-1.06 per 0.1% increase; P < .001). Higher HbA1c during the third trimester was associated with the CC (OR 1.07; 95% CI 1.03-1.10 per 0.1% increase; P < .001). The group defined by a first trimester Hba1c >6.5% (48 mmol/mol) and a third trimester HbA1c <6% was associated with an increased rate of the CC (OR 2.81; 95% CI 1.01-7.86) and an increased rate of LGA (OR 2.20; 95% CI 1.01- 4.78). CONCLUSION: Elevated HbA1c is associated with maternal-fetal complications. Despite optimization of metabolic balance during the third trimester, for patients with early glycemic imbalance the risk of LGA persists.

Defining explicit definitions of potentially inappropriate prescriptions for antidiabetic drugs in patients with type 2 diabetes: A systematic review.

INTRODUCTION: Potentially inappropriate prescriptions (PIPs) of antidiabetic drugs (ADs) (PIPADs) to patients with type 2 diabetes mellitus (T2DM) have been reported in some studies. The detection of PIPs in electronic databases requires the development of explicit definitions. This approach is widely used in geriatrics but has not been extended to PIPADs in diabetes mellitus. The objective of the present literature review was to identify all explicit definitions of PIPADs in patients with T2DM. MATERIALS AND METHODS: We performed a systematic review of the literature listed on Medline (via PubMed), Scopus, Web of Science, and, Embase between 2010 and 2021. The query included a combination of three concepts ("T2DM" AND "PIPs" AND "ADs") and featured a total of 86 keywords. Two independent reviewers selected publications, extracted explicit definitions of PIPADs, and then classified the definitions by therapeutic class and organ class. RESULTS: Of the 4,093 screened publications, 39 were included. In all, 171 mentions of PIPADs (corresponding to 56 unique explicit definitions) were identified. More than 50% of the definitions were related to either metformin (34%) or sulfonylureas (29%). More than 75% of the definitions were related to either abnormal renal function (56%) or age (22%). In addition, 20% (n = 35) mentions stated that biguanides were inappropriate in patients with renal dysfunction and 17.5% (n = 30) stated that sulfonylureas were inappropriate above a certain age. The definitions of PIPADs were heterogeneous and had various degrees of precision. CONCLUSION: Our results showed that researchers focused primarily on the at-risk situations related to biguanide prescriptions in patients with renal dysfunction and the prescription of sulfonylureas to older people. Our systematic review of the literature revealed a lack of consensus on explicit definitions of PIPADs, which were heterogeneous and limited (in most cases) to a small number of drugs and clinical situations.

Prognostic significance of reverse dipping status on lower limb event in type 2 diabetic patients without peripheral arterial disease.

AIMS: We assessed reverse dipping influence on the risk of lower limb events in type 2 diabetic patients without peripheral arterial disease. METHODS: Patients with type 2 diabetes addressed for cardiovascular risk stratification in our university hospital from 2008 to 2012 underwent 24 h blood pressure monitoring. Patients with a prior history of limb revascularization or with a stenosis > 50% of the legs were excluded. Reverse dipping was defined as a greater night-versus day-time systolic blood pressure. The endpoint was the first occurrence of lower limb revascularization or limb amputation. Hazard ratios (HRs) and 95% confidence intervals were calculated using the Cox model. RESULTS: Two hundred and eighty-one patients were included. During a median follow-up of 9.4 [7.7-10.6] years, 20 lower limb events and 45 all-cause deaths were observed. Thirty-five patients were reverse dippers. The reverse dipping status was associated with lower limb events when considering all-cause death as a competitive risk, (HR 3.61 [1.16-11.2], P = 0.026). Reverse dipping, HbA1C and proteinuria were independently associated with lower limb outcome in a multivariable analysis (respectively HR 4.09 [1.29-12.9], P = 0.017, HR 1.30 [1.04-1.63], P = 0.022 and HR 1.06 [1.02-1.11], P = 0.001). CONCLUSIONS: Reverse dipping status is independently associated with worse limb outcome in type 2 diabetic patients.

Multiple symmetric and multiple familial lipomatosis.

Lipomas are the most common soft tissue tumors and are malignant in only 1% of cases. Lipomatosis is defined as the presence of multiple benign lipomas on the body, without lipoatrophy. Their impact on quality of life is significant. Different entities have been described such as symmetrical multiple lipomatosis (MSL), also called Madelung's disease and familial multiple lipomatosis (FML). MSL occurs preferentially in men (but also women) who are alcohol abuser. There are different subtypes of the disease, the most classic of which affects the upper body and the nuchal region with a buffalo hump appearance. A metabolic component with obesity is frequent. In contrast to Dercum's disease, there is no pain. SAOS, complications of the metabolic syndrome and of alcohol abuse including cancers, may be associated and should be screened. FML has been little described in the literature since Brodie's first report in 1846. FML occurs preferentially in the third decade but equally in women and men. Its autosomal dominant component is classically accepted with variable penetrance within the same family. Association with naevi, angiomas, polyneuropathies and with gastrointestinal comorbidities has been reported. Interestingly, and in contrast with most lipodystrophy disorders, the patients show an insulin sensitivity profile. A better understanding of the underlying pathophysiological mechanisms would open up avenues on therapeutic research, since treatments are only symptomatic to date.

Rare Forms of Lipomatosis: Dercum's Disease and Roch-Leri Mesosomatous Lipomatosis.

In contrast to obesity, which is very frequent, lipomatosis and lipodystrophy syndromes are rare diseases of adipose tissue. Lipodystrophy syndromes are characterized by metabolic abnormalities associated with partial or generalized lipoatrophy. Lipomatosis is defined by the presence of several body lipomas without lipoatrophy. Dercum's disease (DD) and Roch-Leri mesosomatous lipomatosis (RLML) are rare and poorly characterized forms of lipomatosis. They have raised little clinical interest despite the non-negligible consequences of DD on quality of life. The main clinical presentation of these diseases includes multiple lipomas, which are painful in DD (in contrast to RLML). The two diseases are frequently associated with obesity and metabolic syndrome, with hypertension, diabetes, or dyslipidemia. The long-term course of the diseases remains poorly described. DD affects mainly women, whereas RLML mostly affects men. In both diseases lipomas are found on the back and thighs, as well as on the abdomen in DD and the forearms in RLML. The painful lipomas tend to recur after surgery in DD (in contrast to RLML). Most cases are sporadic. No specific treatment has been identified, as the pathophysiology remains unknown. Nevertheless, low-grade fat inflammation and specific abnormalities such as hyperbasophilia deserve further investigation. The aim of this review is to analyze the available literature on the topic.