Juris J Meier's research while affiliated with Katholisches Klinikum Bochum and other places
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Publications (228)
Aims:
Gastrointestinal disorders including constipation and fecal incontinence are common in type 2 diabetes and may derive from diabetic autonomous neuropathy, severe intestinal bacterial overgrowth, or a dysfunctional anorectal sphincter. The present study aims to characterize the correlation between these conditions.
Methods:
Patients with ty...
Glucagon‐like peptide‐1 receptor agonists improve glycaemic control: some are now available as oral and subcutaneous formulations, and some have indications for reducing cardiovascular risk. The expanded scope for these therapies warrants comprehensive safety evaluations. We report the safety/tolerability of subcutaneous and oral semaglutide from t...
Cardiovascular outcomes trials (CVOTs) with novel drugs to treat type 2 diabetes have uniformly chosen the composite “major adverse cardiovascular events (MACE)” as their primary endpoint, but they also report hazard ratios for individual cardiovascular outcomes (myocardial infarction, stroke, cardiovascular death, all-cause death, hospitalization...
Background
Individuals with type 1 diabetes and those with depression show differences in the composition of the gut microbiome from that of healthy people. However, these differences have not yet been studied in patients with both diseases. Therefore, we compared the gut microbiome of people with type 1 diabetes with or without depression with mat...
Aims:
To evaluate the efficacy and safety of oral semaglutide versus comparators by patient characteristic subgroups in patients with type 2 diabetes.
Materials and methods:
Change from baseline in HbA1c and body weight, and achievement of HbA1c <7.0% with oral semaglutide 7 mg, 14 mg, flexibly dosed (flex), or comparators were assessed across b...
In clinical practice, the distinction between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) can be challenging, leaving patients with "ambiguous" diabetes type. Insulin-treated patients (n=115) previously diagnosed with T2DM had to be re-classified based on clinical phenotype and laboratory results, and were operationally defi...
Introduction:
Breath tests utilising 13C-labelled substrates for the assessment of gastric emptying have been applied widely. Wagner-Nelson analysis is a pharmacokinetic model that can be utilised to generate a gastric emptying curve from the % 13CO2 measured in breath samples. We compared Wagner-Nelson analysis with (i) scintigraphy and (ii) conv...
Aims:
Impaired renal function is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The goal of this study was to investigate the effect of renal impairment on incretin metabolism in patients with T2DM before and after treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin.
Materials and methods:
Long-stan...
Aims:
The glucagon-like peptide-1 analogue, semaglutide, has been co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, for oral administration. This trial investigated whether upper gastrointestinal (GI) disease had any effect on the exposure of oral semaglutide, an important consideration given that its abs...
IntroductioniGlarLixi, the once-daily fixed-ratio combination of insulin glargine 100 U/ml and lixisenatide, robustly improves glycaemic control in adults with type 2 diabetes irrespective of previous treatment [oral antihyperglycaemic drugs (OADs), basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs)]. Sodium-glucose co-transport...
Obesity is a chronic, multifactorial, relapsing disease. Despite multicomponent lifestyle interventions, including pharmacotherapy, maintaining bodyweight loss is challenging for many people. The pathophysiology of obesity is complex, and currently approved pharmacotherapies only target a few of the many pathways involved; thus, single-targeting ag...
DPP-4 inhibitors may prevent hypoglycemic episodes in insulin-treated type 2 diabetes (T2D), but mechanisms are unclear. 20 T2D patients treated with basal insulin and metformin (± other agents) were recruited for two randomized treatments (placebo or 100 mg/d sitagliptin) in addition to insulin glargine/metformin; 17 completed (3 women, 14 men; ag...
The first clinical study of an oral small-molecule GLP-1 receptor agonist suggests effective glycemic control and weight loss in patients with type 2 diabetes.
Despite the benefits of early and effective glycemic control in the management of type 2 diabetes (T2D), achieving glycated hemoglobin (HbA1c) targets is challenging in some patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide effective reductions in HbA1c and body weight. Semaglutide is the only GLP-1RA that is available in both...
Despite the successful development of new therapies for the treatment of type 2 diabetes, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors, the search for novel treatment options that can provide better glycaemic control and at reduce complications is a continuous effort. The present Review aim...
Aims:
GLP-1 receptor agonists (GLP-1 RAs) promote weight loss, but also gastrointestinal side-effects. The extent of these side-effects may depend on dosing and pharmacokinetic attributes. However, it remains controversial whether GLP-1 RAs differentially affect digestive and pancreatic function and whether gastrointestinal side-effects are correl...
Zusammenfassung
Eine Patientin wurde aufgrund rezidivierender postprandialer Hypoglykämien nach Roux-en-Y-Magenbypass mit Diazoxid behandelt, nachdem eine Ernährungsumstellung keine Symptomlinderung erzielt hatte. Nach Eindosierung von Diazoxid mit guter Akutverträglichkeit wurde die Patientin entlassen. Eine Woche nach Therapieeinleitung kam es zu...
Acute bacterial skin and skin structures infections (ABSSSIs) are associated with high morbidity, costs and mortality in patients with diabetes mellitus. Their appropriate management should include several figures and a well-organized approach. This review aims to highlight the interplay between diabetes and ABSSSIs and bring out the unmet clinical...
Zusammenfassung
Einleitung Pankreasresektionen werden bei schwerwiegenden Pankreaserkrankungen durchgeführt. Bei Komplikationen einer chronischen Pankreatitis, teilweise jedoch auch bei Raumforderungen, kann eine Pankreasteilresektion sinnvoll sein. Eine totale Pankreatektomie führt zum absoluten Insulinmangel und der Notwendigkeit einer Insulinthe...
Objective:
Acute experimental variations in glycemia decelerate (hyperglycemia) or accelerate (hypoglycemia) gastric emptying. Whether spontaneous variations in fasting plasma glucose (FPG) have a similar influence on gastric emptying is yet unclear.
Research design and methods:
Gastric emptying of a mixed meal was prospectively studied three ti...
Background
Basal rate profiles in patients with type 1 diabetes on insulin pump therapy are subject to enormous inter-individual heterogeneity. Tools to predict basal rates based on clinical characteristics may facilitate insulin pump therapy.
Methods
Data from 339 consecutive in-patients with adult type 1 diabetes on insulin pump therapy were col...
Background
GLP-1 receptor agonists (GLP-1 RAs) with exenatide b.i.d. first approved to treat type 2 diabetes in 2005 have been further developed to yield effective compounds/preparations that have overcome the original problem of rapid elimination (short half-life), initially necessitating short intervals between injections (twice daily for exenati...
Purpose:
To compare the efficacy and safety of short- and long-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs), both used in combination with basal insulin, in patients with type 2 diabetes.
Data sources and study selection:
Randomized controlled trials comparing the coadministration of short- or long-acting GLP-1 RAs and basal insu...
Background
Pump-treated patients with type 1 diabetes have widely differing basal insulin infusion profiles. We analyzed consequences of such heterogeneity for glycemic control under fasting conditions.
Methods
Data from 339 adult patients with type 1 diabetes on insulin pump therapy undergoing a 24-hour fast (basal rate test) were retrospectively...
Objective:
Short-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs) decelerate gastric emptying more than long-acting GLP-1 RAs. Delayed gastric emptying is a risk factor for gastroesophageal reflux disease. We aimed to measure esophageal reflux and function as well as gastric emptying and acid secretion during treatment with short-actin...
iGlarLixi, the once-daily fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, has been shown to robustly improve glycemic control in adults with T2D.
To assess the effects of iGlarLixi with SGLT2i in T2D, we conducted subgroup analyses according to SGLT2i use in the following populations: 1) adults uncontrolled on GLP-1 receptor...
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLTi) are widely used to treat type 2 diabetes (T2D) but trial data on their combined use are limited. We report the first data on oral semaglutide in combination with SGLT2i. This was a post-hoc subgroup analysis of the 52-week, double-blind, double-dummy PIONEER 4 trial (N...
Zusammenfassung
Der überwiegende Teil der Patienten mit Typ-2-Diabetes kann im ambulanten Umfeld (Hausarztpraxen und Diabetes-Schwerpunktpraxen) adäquat und kosteneffektiv behandelt werden. Dennoch erreichen trotz guter ambulanter Versorgungsstrukturen ca. 20–30 % der Patienten keine zufriedenstellende Blutzuckereinstellung. In derartigen Fällen ka...
Background
Amyloid deposits are a typical finding in in pancreatic islets from patients with type 2 diabetes. Whether this is linked to the pathogenesis of type 2 diabetes is currently unknown. Therefore, we compared the occurrence of islet amyloid in patients with type 2 diabetes, diabetes secondary to pancreatic disorders and non-diabetic individ...
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended for glycaemic management in patients with type 2 diabetes (T2D). Oral semaglutide, the first oral GLP-1RA, has recently been approved for clinical use, based on the results of the randomised, Phase 3a Peptide InnOvatioN for Early DiabEtes Treatment (PIONEER) clinical trials. The P...
AimsWe aimed to quantify the exposure to physical exercise associated with professional, recreational, or traffic-related activities in patients with type 2 diabetes, which may provoke or aggravate hypoglycaemic episodes, and to assess whether such risks determine the choice of medications minimizing the risk of hypoglycaemia.Methods
In total, 203...
The ever-increasing burden of type 2 diabetes mellitus (T2DM) worldwide, has led to the emergence of several antidiabetes drugs with different modes of action. Incretin hormones and their effect on glucose metabolism and pathogenesis of T2DM has been a landmark discovery in the management of this increasingly prevalent metabolic disorder. Glucagon...
Introduction
Basal-bolus (BB) regimens are generally used to intensify basal insulin therapy in patients with type 2 diabetes (T2D) not meeting glycemic targets. However, drawbacks include multiple injection burden and risk of weight gain and hypoglycemia. A once-daily titratable fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide...
Aim:
To examine the glucose-lowering mechanisms of the glucagon-like peptide-1 receptor agonist lixisenatide after two subsequent meals and in combination with basal insulin.
Materials and methods:
Twenty-eight metformin-treated patients with type 2 diabetes were randomly assigned to treatment sequences with either lixisenatide or insulin glargi...
Background/aims:
Some epidemiological data have suggested an elevated risk for acute pancreatitis and pancreatic cancer after exposure to GLP-1 receptor agonists and DPP-4 inhibitors. Recently, such outcomes have been assessed and adjudicated as adverse events of special interest in cardiovascular outcomes studies.
Methods:
We performed a meta-a...
Background
Twenty-four hour fasting periods are being used to scrutinize basal insulin infusion rates for pump-treated patients with type 1 diabetes.
Methods
Data from 339 consecutive in-patients with adult type 1 diabetes on insulin pump therapy undergoing a 24-hour fast as a basal rate test were retrospectively analyzed. Hourly programmed basal...
Context
Cotadutide is a dual receptor agonist with balanced glucagon-like peptide-1 (GLP-1) and glucagon activity.
Objective
To evaluate different doses of cotadutide and investigate underlying mechanisms for its glucose-lowering effects.
Design/setting
Randomized, double-blind, phase 2a study conducted in two cohorts at five clinical trial sites...
GLP-1, a peptide hormone secreted from the gut stimulating insulin and suppressing glucagon secretion was identified as a parent compound for novel treatments of diabetes, but was degraded (dipeptidyl peptidase-4) eliminated (mainly kidneys) too fast (half-life 1-2 min) to be useful as a therapeutic agent. GLP-1 receptor agonist have been used to t...
Background/Aims The aim of this study was to identify clinical characteristics that distinguish patients who achieve sufficient glycaemic control with basal insulin and oral glucose-lowering medications from those who need treatment intensification.
Patients/Methods 213 out of 1 042 consecutively hospitalized type 2-diabetic patients were treated w...
Oral semaglutide was non-inferior to subcutaneous liraglutide and superior to placebo in
decreasing HbA1c, and superior in decreasing bodyweight compared with both liraglutide and placebo at week 26.
Safety and tolerability of oral semaglutide were similar to subcutaneous liraglutide. Use of oral semaglutide could potentially lead to earlier initia...
Non-adherence to treatment recommendations for patients with diabetes is widespread. This applies to medication as well as recommendations for a healthy lifestyle with appropriate physical activity, a healthy diet, and, if necessary, an end to smoking and weight control. Disregard of these recommendations has been shown to increase the risk of diab...
The GLP-1 analog semaglutide has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) to allow oral administration. Since oral semaglutide is absorbed in the stomach, the effect of upper gastrointestinal disease (UGD) on exposure to oral semaglutide has been investigated in an open-label, parallel-g...
Background: MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1/glucagon receptor activity under development for type 2 diabetes mellitus (T2DM). GLP-1 has been shown to promote glucose-dependent insulin release, delay gastric emptying, and suppress appetite. Glucagon has similar effects on appetite and gastric emptying and enhances energ...
Background: MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1/glucagon receptor activity under development for type 2 diabetes mellitus (T2DM). GLP-1 and glucagon promote delayed gastric emptying, and GLP-1 tolerance has been described.
Methods: This exploratory part of a double-blind phase 2a study measured gastric emptying time (GET)...
Patients (pts) with T2D uncontrolled on metformin ± SGLT2i were randomized to oral semaglutide (sema) 14 mg once daily (N=285), liraglutide (lira) 1.8 mg (N=284) or placebo (pbo, N=142) in a phase 3a, 52-week, double-blind, double-dummy trial (NCT02863419). Endpoints: Change (baseline to week 26) in HbA1c (primary) and body weight (BW, confirmatory...
Background: MEDI0382 is an oxyntomodulin-like peptide with GLP-1/glucagon receptor activity under development for type 2 diabetes mellitus (T2DM). Continuous glucose monitoring (CGM) is valuable for evaluating glucose-lowering efficacy.
Methods: As an exploratory part of a double-blind phase 2a study, CGM was performed for 52 days with a Freestyle...
Background
Procedures suitable for preoperative localization of insulinomas are widely used but it is unclear whether they determine surgical success. We wanted to clarify whether preoperative localization or intraoperative ultrasound determines the success of surgically identifying and removing insulinomas.
Methods
We performed a systematic liter...
Background
Near‐infrared spectroscopy (NIRS) is a non‐invasive method to measure regional tissue oxygenation (rSO2). In patients with atrial fibrillation (AF), cardiac output and endothelial function are altered. Peripheral tissue oxygenation may therefore be reduced. This study aims to describe the peripheral tissue oxygenation of the feet before...
Diabetes is becoming one of the most widespread health burning problems in the elderly. Worldwide prevalence of diabetes among subjects over 65 years was 123 million in 2017, a number that is expected to double in 2045. Old patients with diabetes have a higher risk of common geriatric syndromes, including frailty, cognitive impairment and dementia,...
Examples of replicating islet endocrine cells in a fetal and an infant donor. Pancreatic sections from a fetal (A) and an infant (B) donor immunostained for Endocrine cocktail (insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin) (white), chromograninA (green), Ki67 (red), and DAPI (blue). Yellow arrows showing Ki67 positive endocri...
A rare example of replicating chromograninA positive hormone-negative (CPHN) cells in a fetal and an infant donor. Pancreatic sections from a fetal (A) and an infant (B) donor immunostained for Endocrine cocktail (insulin, glucagon, somatostatin, pancreatic polypeptide, and ghrelin) (white), chromograninA (green), Ki67 (red), and DAPI (blue). Yello...
Human pancreatic development 3. A low power view of child pancreas, 6 years old (A) and 10 years old (B), stained by immunohistochemistry for Insulin (pink), Glucagon (blue), and Ki67 (brown) with a hematoxylin counterstain. Insets, high power images of the indicated area marked by black squares in the low power images. Scale bars, 200 μm in low po...
Chromogranin A positive hormone-negative (CPHN) cells located in the pancreatic ducts do not replicate during fetal and infant life. Pancreatic ducts shown in tissue sections from fetal (A) and infant (B) donors immunostained for Endocrine cocktail (insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin) (white), chromograninA (green),...
Replication of endocrine cells. Quantification of endocrine cell replication shown as percentage of Ki67 positive endocrine cells, immunostained with endocrine cocktail antibodies. Endocrine cell replication diminishes in the pancreas with age (p < 0.05).
Clinical characteristics of nPOD fetal and infant donors for Ki67, Nkx2.2 and Nkx6.1 analysis. PH, pancreas head; PB, pancreas body; PT, pancreas tail.
Percent changes of CPHN cells (positive for either NKx6.1 or NKx2.2) in different compartments of fetal and infant/child pancreas with age: The percentage of either NKX6.1+ or NKX2.2+ CPHN cells (of total CPHN cells in fetal and infant/child cases) found in overall compartments (A,E), within islets (B,F), in cluster cells (C,G) or in single cells (...
Clinical characteristics of nPOD fetal and infant cases for Ki67 and hormone expression analysis in pancreatic ducts. PH, pancreas head; PB, pancreas body; PT, pancreas tail.
Human pancreatic development 2. A low power view of pancreas from young children, 2 years old (A) and 3.6 years old (B), stained by immunohistochemistry for Insulin (pink), Glucagon (blue) and Ki67 (brown) with a hematoxylin counterstain. Insets, high power images of the indicated area marked by black squares in the low power images. Scale bars, 20...
NKX6.1 + and NKX2.2 + CPHN cells detected in differentcompartments of the pancreas in fetal and infant donors.
Context: Previously, we identified chromograninA positive hormone-negative (CPHN) cells in high frequency in human fetal and neonatal pancreas, likely representing nascent endocrine precursor cells. Here, we characterize the putative endocrine fate and replicative status of these newly formed cells.
Objective: To establish the replicative frequency...
Human pancreatic development 1. A low power view of fetal pancreas (A) and infant pancreas (B) stained by immunohistochemistry for Insulin (pink), Glucagon (blue), and Ki67 (brown) with a hematoxylin counterstain. Insets, high power images of the indicated area marked by black squares in the low power images. Scale bars, 200 μm in low power images...
Clinical characteristic of fetal and infant cases used for quantification of CPHN cells. PT, pancreas tail.
Replication and expression of pan-endocrine hormones in cells in the ducts and PDGs of fetal and infant pancreas. Representative pancreatic sections from fetal and infant donors stained for Ki67/Hematoxylin (A,B, respectively) and Insulin/PP/hematoxylin (C,D, respectively). Insets, higher magnification of selected areas (indicated by black squares)...
An excess heart failure (HF) risk persists in patients with type 2 diabetes (T2D) despite optimal control of an array of conventional risk factors, including hyperglycaemia. Twelve cardiovascular outcome trials (CVOTs) have been so far published, although none, with the exception of DECLARE with dapagliflozin, has included HF in the primary endpoin...
Table S1. Study designs.
Table S2. Key efficacy and safety outcomes.
Table S3. Reductions in FPG and PPG.
Aim
Simultaneous treatment with insulin glargine 100 U (iGlar) and the glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) lixisenatide (Lixi) as a single‐pen, titratable, fixed‐ratio combination (iGlarLixi) is a new option for patients with type 2 diabetes (T2D) initiating or intensifying basal insulin. Two exploratory analyses indirectly compared...
Incretin hormones are gut peptides that are secreted after nutrient intake and stimulate insulin secretion together with hyperglycaemia. GIP (glucose-dependent insulinotropic polypeptide) und GLP-1 (glucagon-like peptide-1) are the known incretin hormones from the upper (GIP, K cells) and lower (GLP-1, L cells) gut. Together, they are responsible f...
Potentiation of glucagon-like peptide-1 (GLP-1) action through selective GLP-1 receptor (GLP-1R) agonism or by prevention of enzymatic degradation by inhibition of dipeptidyl peptidase-4 (DPP-4) promotes glycemic reduction for the treatment of type 2 diabetes mellitus by glucose-dependent control of insulin and glucagon secretion. GLP-1R agonists a...
Objective:
Diabetes frequently develops in patients with chronic pancreatitis. We examined the alterations in the glucagon response to hypoglycemia and to oral glucose administration in patients with diabetes due to chronic pancreatitis.
Research design and methods:
Ten patients with diabetes secondary to chronic pancreatitis were compared with...
Beta-cell function can be enhanced by direct stimulation of insulin secretion or by induction of beta-cell rest. Whether both strategies can complement each other has not yet been examined. 28 subjects with type 2 diabetes (HbA1c 7.8 ± 0.5 %) were treated with either lixisenatide or titrated insulin glargine, followed by their combined administrati...
Incretin-based medications (glucagon-like peptide-1 [GLP-1] receptor agonists and inhibitors of dipeptidyl peptidase-4 [DPP-4] are glucose-lowering drugs approved and introduced after 2006 (1). Although both classes of drugs appeared to be relatively safe based on results from clinical trials and standard animal toxicology studies, epidemiological...
Aims/hypothesis:
Basal rate tests (24 h fasting periods) may be necessary to optimize basal insulin replacement in type 1 diabetes. It was the aim to prospectively compare allowing negligible carbohydrate snacks versus absolute fasting.
Methods:
20 patients with type 1 diabetes (age 48 ± 15 years; 9 women, 11 men; BMI 28.5 ± 4.5 kg/m(2) ; HbA1c...
Introduction:
Determining the dignity of intraductal papillary mucinous neoplasms (IPMNs) by imaging procedures is challenging. Various CT-based criteria were evaluated.
Patients and methods:
Preoperative CT scans from 47 patients with IPMN were analyzed. Predefined criteria of malignancy were compared between patients with benign (bIPMN; n = 28...
Objective:
To evaluate the efficacy and safety of empagliflozin versus placebo as add-on therapy in patients with type 2 diabetes and inadequate glycemic control with linagliptin and metformin.
Research design and methods:
Patients with HbA1c ≥8.0% and ≤10.5% (≥64 and ≤91 mmol/mol) while receiving stable-dose metformin received open-label linagl...
Treatment of type 2 diabetes mellitus with GLP1 receptor agonists can result in long-term glycaemic control or can fail over time, in which case insulin can be used as an alternative or as an additive treatment. New research shows that the latter is more likely to achieve glycaemic targets than the former.
Aim:
GLP-1 receptor agonists (RAs) may cause nausea, vomiting or diarrhoea. The purpose was to assess the risk of adverse events (AEs) with GLP-1 RAs and their relation to dose, background medication and duration of action.
Material and methods:
The PubMed database was searched and 32 clinical trials with GLP-1 RAs (phase 3) were selected. We pe...
Aims:
To study differences in clinical outcomes between initiating glucagon-like peptide-1 receptor agonist (GLP-1 RAs) vs. insulin treatment in patients with type 2 diabetes treated with oral glucose-lowering medications (OGLM).
Methods:
Prospective, randomized trials comparing GLP-1 RA and insulin treatment head-to-head as add-on to OGLM were...