Econstudentlog

The Ice Age (I)

I’m currently reading this book. Some observations and links related to the first half of the book below:

“It is important to appreciate from the outset that the Quaternary ice age was not one long episode of unremitting cold climate. […] By exploring the landforms, sediments, and fossils of the Quaternary Period we can identify glacials: periods of severe cold climate when great ice sheets formed in the high middle latitudes of the northern hemisphere and glaciers and ice caps advanced in mountain regions around the world. We can also recognize periods of warm climate known as interglacials when mean air temperatures in the middle latitudes were comparable to, and sometimes higher than, those of the present. As the climate shifted from glacial to interglacial mode, the large ice sheets of Eurasia and North America retreated allowing forest biomes to re-colonize the ice free landscapes. It is also important to recognize that the ice age isn’t just about advancing and retreating ice sheets. Major environmental changes also took place in the Mediterranean region and in the tropics. The Sahara, for example, became drier, cooler, and dustier during glacial periods yet early in the present interglacial it was a mosaic of lakes and oases with tracts of lush vegetation. A defining feature of the Quaternary Period is the repeated fluctuation in climate as conditions shifted from glacial to interglacial, and back again, during the course of the last 2.5 million years or so. A key question in ice age research is why does the Earth’s climate system shift so dramatically and so frequently?”

“Today we have large ice masses in the Polar Regions, but a defining feature of the Quaternary is the build-up and decay of continental-scale ice sheets in the high middle latitudes of the northern hemisphere. […] the Laurentide and Cordilleran ice sheets […] covered most of Canada and large tracts of the northern USA during glacial stages. Around 22,000 years ago, when the Laurentide ice sheet reached its maximum extent during the most recent glacial stage, it was considerably larger in both surface area and volume (34.8 million km3) than the present-day East and West Antarctic ice sheets combined (27 million km3). With a major ice dome centred on Hudson Bay greater than 4 km thick, it formed the largest body of ice on Earth. This great mass of ice depressed the crust beneath its bed by many hundreds of metres. Now shed of this burden, the crust is still slowly recovering today at rates of up to 1 cm per year. Glacial ice extended out beyond the 38th parallel across the lowland regions of North America. Chicago, Boston, and New York all lie on thick glacial deposits left by the Laurentide ice sheet. […] With huge volumes of water locked up in the ice sheets, global sea level was about 120 m lower than present at the Last Glacial Maximum (LGM), exposing large expanses of continental shelf and creating land bridges that allowed humans, animals, and plants to move between continents. Migration from eastern Russia to Alaska, for example, was possible via the Bering land bridge.”

“Large ice sheets also developed in Europe. […] The British Isles lie in an especially sensitive location on the Atlantic fringe of Europe between latitudes 50 and 60° north. Because of this geography, the Quaternary deposits of Britain record especially dramatic shifts in environmental conditions. The most extensive glaciation saw ice sheets extend as far south as the Thames Valley with wide braided rivers charged with meltwater and sediment from the ice margin. Beyond the glacial ice much of southern Britain would have been a treeless, tundra steppe environment with tracts of permanently frozen ground […]. At the LGM […] [t]he Baltic and North Seas were dry land and Britain was connected to mainland Europe. Beyond the British and Scandinavian ice sheets, much of central and northern Europe was a treeless tundra steppe habitat. […] During warm interglacial stages […] [b]road-leaved deciduous woodland with grassland was the dominant vegetation […]. In the warmest parts of interglacials thermophilous […] insects from the Mediterranean were common in Britain whilst the large mammal fauna of the Last Interglacial (c.130,000 to 115,000 years ago) included even more exotic species such as the short tusked elephant, rhinoceros, and hippopotamus. In some interglacials, the rivers of southern Britain contained molluscs that now live in the Nile Valley. For much of the Quaternary, however, climate would have been in an intermediate state (either warming or cooling) between these glacial and interglacial extremes.”

“Glaciologists make a distinction between three main types of glacier (valley glaciers, ice caps, and ice sheets) on the basis of scale and topographic setting. A glacier is normally constrained by the surrounding topography such as a valley and has a clearly defined source area. An ice cap builds up as a dome-like form on a high plateau or mountain peak and may feed several outlet glaciers to valleys below. Ice sheets notionally exceed 50,000 km2 and are not constrained by topography.”

“We live in unusual times. For more than 90 per cent of its 4.6-billion-year history, Earth has been too warm — even at the poles — for ice sheets to form. Ice ages are not the norm for our planet. Periods of sustained (over several million years) large-scale glaciation can be called glacial epochs. Tillites in the geological record tells us that the Quaternary ice age is just one of at least six great glacial epochs that have taken place over the last three billion years or so […]. The Quaternary itself is the culmination of a much longer glacial epoch that began around 35 million years ago (Ma) when glaciers and ice sheets first formed in Antarctica. This is known as the Cenozoic glacial epoch. There is still much to learn about these ancient glacial epochs, especially the so-called Snowball Earth states of the Precambrian (before 542 Ma) when the boundary conditions for the global climate system were so different to those of today. […] This book is concerned with the Quaternary ice age – it has the richest and most varied records of environmental change. Because its sediments are so recent they have not been subjected to millions of years of erosion or deep burial and metamorphism. […] in aquatic settings, such as lakes and peat bogs, organic materials such as insects, leaves, and seeds, as well as microfossils such as pollen and fungal spores can be exceptionally well preserved in the fossil record. This allows us to create very detailed pictures of past ecosystems under glacial and interglacial conditions. This field of research is known as Quaternary paeloecology.”

“An erratic […] is a piece of rock that has been transported from its place of origin. […] Many erratics stand out because they lie on bedrock that is very different to their source. […] Erratics are normally associated with transport by glaciers or ice sheets, but in the early 19th century mechanisms such as the great deluge or rafting on icebergs were commonly invoked. […] Enormous erratic boulders […] were well known to 18th- and 19th-centery geologists. […] Their origin was a source of lively and protracted debate […] Early observers of Alpine glaciers had noted the presence of large boulders on the surface of active glaciers or forming part of the debris pile at the glacier snout. These were readily explainable, but erratic boulders had long been noted in locations that defied rational explanations. The erratics found at elevations far above their known sources, and in places such as Britain where glaciers were absent, were especially problematic for early students of landscape history. […] A huge deluge […] was commonly invoked to explain the disposition of such boulders and many saw them as more hard evidence in support of the Biblical flood. […] At this time, the Church of England held a strong influence over much of higher education and especially so in Cambridge and Oxford.”

Venetz [in the early 19th century] produced remarkably detailed topographic maps of lateral and terminal moraines that lay far down valley of the modern glaciers. He was able to show that many glaciers had advanced and retreated in the historical period. His was the first systematic analysis of climate-glacier-landscape interactions. […] In 1821, Venetz presented his findings to the Société Helvétiques des Sciences Naturelles, setting out Perraudin’s ideas alongside his own. The paper had little impact, however, and would not see publication until 1833. […] Jean de Charpentier [in his work] paid particular attention to the disposition of large erratic blocks and the occurrence of polished and striated bedrock surfaces in the deep valleys of western Switzerland. A major step forward was Charpentier’s recognition of a clear relationship between the elevation of the erratic blocks in the Rhône Valley and the vertical extent of glacially smoothed rock walls. He noted that the bedrock valley sides above the erratic blocks were not worn smooth because they must have been above the level of the ancient glacier surface. The rock walls below the erratics always bore the hallmarks of contact with glacial ice. We call this boundary the trimline. It is often clearly marked in hard bedrock because the texture of the valley sides above the glacier surface is fractured due to attack by frost weathering. The detachment of rock particles above the trimline adds debris to lateral moraines and the glacier surface. These insights allowed Charpentier to reconstruct the vertical extent of former glaciers for the first time. Venetz and Perraudin had already shown how to demarcate the length and width of glaciers using the terminal and lateral moraines in these valleys. Charpentier described some of the most striking erratic boulders in the Alps […]. As Charpentier mapped the giant erratics, polished bedrock surfaces, and moraines in the Rhône Valley, it became clear to him that the valley must once have been occupied by a truly enormous glacier or ‘glacier-monstre’ as he called it. […] In 1836, Charpentier published a key paper setting out the main findings of their [his and Venetz’] glacial work”.

“Even before Charpentier was thinking about large ice masses in Switzerland, Jens Esmark (1763-1839) […] had suggested that northern European glaciers had been much more extensive in the past and were responsible for the transport of large erratic boulders and the formation of moraines. Esmark also recognized the key role of deep bedrock erosion by glacial ice in the formation of the spectacular Norwegian fjords. He worked out that glaciers in Norway had once extended down to sea level. Esmark’s ideas were […] translated into English and published […] in 1826, a decade in advance of Charpentier’s paper. Esmark discussed a large body of evidence pointing to an extensive glaciation of northern Europe. […] his thinking was far in advance of his contemporaries […] Unfortunately, even Esmark’s carefully argued paper held little sway in Britain and elsewhere […] it would be many decades before there was general acceptance within the geological community that glaciers could spread out across low gradient landscapes. […] in the lecture theatres and academic societies of Paris, Berlin, and London, the geological establishment was slow to take up these ideas, even though they were published in both English and French and were widely available. Much of the debate in the 1820s and early 1830s centred on the controversy over the evolution of valleys between the fluvialists (Hutton, Playfair, and others), who advocated slow river erosion, and the diluvialists (Buckland, De la Beche, and others) who argued that big valleys and large boulders needed huge deluges. The role of glaciers in valley and fjord formation was not considered. […] The key elements of a glacial theory were in place but nobody was listening. […] It would be decades before a majority accepted that vast tracts of Eurasia and North America had once been covered by mighty ice sheets.”

“Most geologists in 1840 saw Agassiz’s great ice sheet as a retrograde step. It was just too catastrophist — a blatant violation of hard-won uniformitarian principles. It was the antithesis of the new rational geology and was not underpinned by carefully assembled field data. So, for many, as an explanation for the superficial deposits of the Quaternary, it was no more convincing than the deluge. […] Ancient climates were [also] supposed to be warmer not colder. The suggestion of a freezing glacial epoch in the recent geological past, followed by the temperate climate of the present, still jarred with the conventional wisdom that Earth history, from its juvenile molten state to the present, was an uninterrupted record of long-term cooling without abrupt change. Lyell’s drift ice theory [according to which erratics (and till) had been transported by icebergs drifting in water, instead of glaciers transporting the material over land – US] also provided an attractive alternative to Agassiz’s ice age because it did not demand a period of cold glacial climate in areas that now enjoy temperate conditions. […] If anything, the 1840 sessions at the Geological Society had galvanized support for floating ice as a mechanism for drift deposition in the lowlands. Lyell’s model proved to be remarkably resilient—its popularity proved to be the major obstacle to the wider adoption of the land ice theory. […] many refused to believe that glacier ice could advance across gently sloping lowland terrain. This was a reasonable objection at this time since the ice sheets of Greenland and Antarctica had not yet been investigated from a glaciological point of view. It is not difficult to understand why many British geologists rejected the glacial theory when the proximity and potency of the sea was so obvious and nobody knew how large ice sheets behaved.”

Hitchcock […] was one of the first Americans to publicly embrace Agassiz’s ideas […] but he later stepped back from a full endorsement, leaving a role for floating ice. This hesitant beginning set the tone for the next few decades in North America as its geologists began to debate whether they could see the work of ice sheets or icebergs. There was a particularly strong tradition of scriptural geology in 19th-century North America. Its practitioners attempted to reconcile their field observations with the Bible and there were often close links with like-minded souls in Britain. […] If the standing of Lyell extended the useful lifespan of the iceberg theory, it was gradually worn down by a growing body of field evidence from Europe and North America that pointed to the action of glacier ice. […] The continental glacial theory prevailed in North America because it provided a much better explanation for the vast majority of the features recorded in the landscape. The striking regularity and fixed alignment of many features could not be the work of icebergs whose wanderings were governed by winds and ocean currents. The southern limit of the glacial deposits is often marked by pronounced ridges in an otherwise low-relief landscape. These end moraines mark the edge of the former ice sheet and they cannot be formed by floating ice. It took a long time to put all the pieces of evidence together in North America because of the vast scale of the territory to be mapped. Once the patterns of erratic dispersal, large-scale scratching of bedrock, terminal moraines, drumlin fields, and other features were mapped, their systematic arrangement argued strongly against the agency of drifting ice. Unlike their counterparts in Britain, who were never very far from the sea, geologists working deep in the continental interior of North America found it much easier to dismiss the idea of a great marine submergence. Furthermore, icebergs just did not transport enough sediment to account for the enormous extent and great thickness of the Quaternary deposits. It was also realized that icebergs were just not capable of planing off hard bedrock to create plateau surfaces. Neither were they able to polish, scratch, or cut deep grooves into ancient bedrock. All these features pointed to the action of land-based glacial ice. Slowly, but surely, the reality of vast expanses of glacier ice covering much of Canada and the northern states of the USA became apparent.”

Links:

Quaternary.
The Parallel Roads of Glen Roy.
William Boyd Dawkins.
Adams mammoth.
Georges Cuvier.
Cryosphere.
Cirque (geology). Arête. Tarn. Moraine. Drumlin. Till/Tillite. Glacier morphology.
James Hutton.
William Buckland.
Diluvium.
Charles Lyell.
Giétro Glacier.
Cwm Idwal.
Timothy Abbott Conrad. Charles Whittlesey. James Dwight Dana.

February 23, 2018 Posted by | Books, Ecology, Geography, Geology, History, Paleontology | Leave a comment

A few (more) diabetes papers of interest

Earlier this week I covered a couple of papers, but the second paper turned out to include a lot of interesting stuff so I decided to cut the post short and postpone my coverage of the other papers I’d intended to cover in that post until a later point in time; this post includes some of those other papers I’d intended to cover in that post.

i. TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes.

“Although the autoimmune destruction of β-cells has a major role in the development of type 1 diabetes, there is growing evidence that the differences in clinical, metabolic, immunologic, and genetic characteristics among patients (1) likely reflect diverse etiology and pathogenesis (2). Factors that govern this heterogeneity are poorly understood, yet these may have important implications for prognosis, therapy, and prevention.

The transcription factor 7 like 2 (TCF7L2) locus contains the single nucleotide polymorphism (SNP) most strongly associated with type 2 diabetes risk, with an ∼30% increase per risk allele (3). In a U.S. cohort, heterozygous and homozygous carriers of the at-risk alleles comprised 40.6% and 7.9%, respectively, of the control subjects and 44.3% and 18.3%, respectively, of the individuals with type 2 diabetes (3). The locus has no known association with type 1 diabetes overall (48), with conflicting reports in latent autoimmune diabetes in adults (816). […] Our studies in two separate cohorts have shown that the type 2 diabetes–associated TCF7L2 genetic variant is more frequent among specific subsets of individuals with autoimmune type 1 diabetes, specifically those with fewer markers of islet autoimmunity (22,23). These observations support a role of this genetic variant in the pathogenesis of diabetes at least in a subset of individuals with autoimmune diabetes. However, whether individuals with type 1 diabetes and this genetic variant have distinct metabolic abnormalities has not been investigated. We aimed to study the immunologic and metabolic characteristics of individuals with type 1 diabetes who carry a type 2 diabetes–associated allele of the TCF7L2 locus.”

“We studied 810 TrialNet participants with newly diagnosed type 1 diabetes and found that among individuals 12 years and older, the type 2 diabetes–associated TCF7L2 genetic variant is more frequent in those presenting with a single autoantibody than in participants who had multiple autoantibodies. These TCF7L2 variants were also associated with higher mean C-peptide AUC and lower mean glucose AUC levels at the onset of type 1 diabetes. […] These findings suggest that, besides the well-known link with type 2 diabetes, the TCF7L2 locus may play a role in the development of type 1 diabetes. The type 2 diabetes–associated TCF7L2 genetic variant identifies a subset of individuals with autoimmune type 1 diabetes and fewer markers of islet autoimmunity, lower glucose, and higher C-peptide at diagnosis. […] A possible interpretation of these data is that TCF7L2-encoded diabetogenic mechanisms may contribute to diabetes development in individuals with limited autoimmunity […]. Because the risk of progression to type 1 diabetes is lower in individuals with single compared with multiple autoantibodies, it is possible that in the absence of this type 2 diabetes–associated TCF7L2 variant, these individuals may have not manifested diabetes. If that is the case, we would postulate that disease development in these patients may have a type 2 diabetes–like pathogenesis in which islet autoimmunity is a significant component but not necessarily the primary driver.”

“The association between this genetic variant and single autoantibody positivity was present in individuals 12 years or older but not in children younger than 12 years. […] The results in the current study suggest that the type 2 diabetes–associated TCF7L2 genetic variant plays a larger role in older individuals. There is mounting evidence that the pathogenesis of type 1 diabetes varies by age (31). Younger individuals appear to have a more aggressive form of disease, with faster decline of β-cell function before and after onset of disease, higher frequency and severity of diabetic ketoacidosis, which is a clinical correlate of severe insulin deficiency, and lower C-peptide at presentation (3135). Furthermore, older patients are less likely to have type 1 diabetes–associated HLA alleles and islet autoantibodies (28). […] Taken together, we have demonstrated that individuals with autoimmune type 1 diabetes who carry the type 2 diabetes–associated TCF7L2 genetic variant have a distinct phenotype characterized by milder immunologic and metabolic characteristics than noncarriers, closer to those of type 2 diabetes, with an important effect of age.”

ii. Heart Failure: The Most Important, Preventable, and Treatable Cardiovascular Complication of Type 2 Diabetes.

“Concerns about cardiovascular disease in type 2 diabetes have traditionally focused on atherosclerotic vasculo-occlusive events, such as myocardial infarction, stroke, and limb ischemia. However, one of the earliest, most common, and most serious cardiovascular disorders in patients with diabetes is heart failure (1). Following its onset, patients experience a striking deterioration in their clinical course, which is marked by frequent hospitalizations and eventually death. Many sudden deaths in diabetes are related to underlying ventricular dysfunction rather than a new ischemic event. […] Heart failure and diabetes are linked pathophysiologically. Type 2 diabetes and heart failure are each characterized by insulin resistance and are accompanied by the activation of neurohormonal systems (norepinephrine, angiotensin II, aldosterone, and neprilysin) (3). The two disorders overlap; diabetes is present in 35–45% of patients with chronic heart failure, whether they have a reduced or preserved ejection fraction.”

“Treatments that lower blood glucose do not exert any consistently favorable effect on the risk of heart failure in patients with diabetes (6). In contrast, treatments that increase insulin signaling are accompanied by an increased risk of heart failure. Insulin use is independently associated with an enhanced likelihood of heart failure (7). Thiazolidinediones promote insulin signaling and have increased the risk of heart failure in controlled clinical trials (6). With respect to incretin-based secretagogues, liraglutide increases the clinical instability of patients with existing heart failure (8,9), and the dipeptidyl peptidase 4 inhibitors saxagliptin and alogliptin are associated with an increased risk of heart failure in diabetes (10). The likelihood of heart failure with the use of sulfonylureas may be comparable to that with thiazolidinediones (11). Interestingly, the only two classes of drugs that ameliorate hyperinsulinemia (metformin and sodium–glucose cotransporter 2 inhibitors) are also the only two classes of antidiabetes drugs that appear to reduce the risk of heart failure and its adverse consequences (12,13). These findings are consistent with experimental evidence that insulin exerts adverse effects on the heart and kidneys that can contribute to heart failure (14). Therefore, physicians can prevent many cases of heart failure in type 2 diabetes by careful consideration of the choice of agents used to achieve glycemic control. Importantly, these decisions have an immediate effect; changes in risk are seen within the first few months of changes in treatment. This immediacy stands in contrast to the years of therapy required to see a benefit of antidiabetes drugs on microvascular risk.”

“As reported by van den Berge et al. (4), the prognosis of patients with heart failure has improved over the past two decades; heart failure with a reduced ejection fraction is a treatable disease. Inhibitors of the renin-angiotensin system are a cornerstone of the management of both disorders; they prevent the onset of heart failure and the progression of nephropathy in patients with diabetes, and they reduce the risk of cardiovascular death and hospitalization in those with established heart failure (3,15). Diabetes does not influence the magnitude of the relative benefit of ACE inhibitors in patients with heart failure, but patients with diabetes experience a greater absolute benefit from treatment (16).”

“The totality of evidence from randomized trials […] demonstrates that in patients with diabetes, heart failure is not only common and clinically important, but it can also be prevented and treated. This conclusion is particularly significant because physicians have long ignored heart failure in their focus on glycemic control and their concerns about the ischemic macrovascular complications of diabetes (1).”

iii. Closely related to the above study: Mortality Reduction Associated With β-Adrenoceptor Inhibition in Chronic Heart Failure Is Greater in Patients With Diabetes.

“Diabetes increases mortality in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction. Studies have questioned the safety of β-adrenoceptor blockers (β-blockers) in some patients with diabetes and reduced left ventricular ejection fraction. We examined whether β-blockers and ACE inhibitors (ACEIs) are associated with differential effects on mortality in CHF patients with and without diabetes. […] We conducted a prospective cohort study of 1,797 patients with CHF recruited between 2006 and 2014, with mean follow-up of 4 years.”

RESULTS Patients with diabetes were prescribed larger doses of β-blockers and ACEIs than were patients without diabetes. Increasing β-blocker dose was associated with lower mortality in patients with diabetes (8.9% per mg/day; 95% CI 5–12.6) and without diabetes (3.5% per mg/day; 95% CI 0.7–6.3), although the effect was larger in people with diabetes (interaction P = 0.027). Increasing ACEI dose was associated with lower mortality in patients with diabetes (5.9% per mg/day; 95% CI 2.5–9.2) and without diabetes (5.1% per mg/day; 95% CI 2.6–7.6), with similar effect size in these groups (interaction P = 0.76).”

“Our most important findings are:

  • Higher-dose β-blockers are associated with lower mortality in patients with CHF and LVSD, but patients with diabetes may derive more benefit from higher-dose β-blockers.

  • Higher-dose ACEIs were associated with comparable mortality reduction in people with and without diabetes.

  • The association between higher β-blocker dose and reduced mortality is most pronounced in patients with diabetes who have more severely impaired left ventricular function.

  • Among patients with diabetes, the relationship between β-blocker dose and mortality was not associated with glycemic control or insulin therapy.”

“We make the important observation that patients with diabetes may derive more prognostic benefit from higher β-blocker doses than patients without diabetes. These data should provide reassurance to patients and health care providers and encourage careful but determined uptitration of β-blockers in this high-risk group of patients.”

iv. Diabetes, Prediabetes, and Brain Volumes and Subclinical Cerebrovascular Disease on MRI: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

“Diabetes and prediabetes are associated with accelerated cognitive decline (1), and diabetes is associated with an approximately twofold increased risk of dementia (2). Subclinical brain pathology, as defined by small vessel disease (lacunar infarcts, white matter hyperintensities [WMH], and microhemorrhages), large vessel disease (cortical infarcts), and smaller brain volumes also are associated with an increased risk of cognitive decline and dementia (37). The mechanisms by which diabetes contributes to accelerated cognitive decline and dementia are not fully understood, but contributions of hyperglycemia to both cerebrovascular disease and primary neurodegenerative disease have been suggested in the literature, although results are inconsistent (2,8). Given that diabetes is a vascular risk factor, brain atrophy among individuals with diabetes may be driven by increased cerebrovascular disease. Brain magnetic resonance imaging (MRI) provides a noninvasive opportunity to study associations of hyperglycemia with small vessel disease (lacunar infarcts, WMH, microhemorrhages), large vessel disease (cortical infarcts), and brain volumes (9).”

“Overall, the mean age of participants [(n = 1,713)] was 75 years, 60% were women, 27% were black, 30% had prediabetes (HbA1c 5.7 to <6.5%), and 35% had diabetes. Compared with participants without diabetes and HbA1c <5.7%, those with prediabetes (HbA1c 5.7 to <6.5%) were of similar age (75.2 vs. 75.0 years; P = 0.551), were more likely to be black (24% vs. 11%; P < 0.001), have less than a high school education (11% vs. 7%; P = 0.017), and have hypertension (71% vs. 63%; P = 0.012) (Table 1). Among participants with diabetes, those with HbA1c <7.0% versus ≥7.0% were of similar age (75.4 vs. 75.1 years; P = 0.481), but those with diabetes and HbA1c ≥7.0% were more likely to be black (39% vs. 28%; P = 0.020) and to have less than a high school education (23% vs. 16%; P = 0.031) and were more likely to have a longer duration of diabetes (12 vs. 8 years; P < 0.001).”

“Compared with participants without diabetes and HbA1c <5.7%, those with diabetes and HbA1c ≥7.0% had smaller total brain volume (β −0.20 SDs; 95% CI −0.31, −0.09) and smaller regional brain volumes, including frontal, temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus (all P < 0.05) […]. Compared with participants with diabetes and HbA1c <7.0%, those with diabetes and HbA1c ≥7.0% had smaller total brain volume (P < 0.001), frontal lobe volume (P = 0.012), temporal lobe volume (P = 0.012), occipital lobe volume (P = 0.008), parietal lobe volume (P = 0.015), deep gray matter volume (P < 0.001), Alzheimer disease signature region volume (0.031), and hippocampal volume (P = 0.016). Both participants with diabetes and HbA1c <7.0% and those with prediabetes (HbA1c 5.7 to <6.5%) had similar total and regional brain volumes compared with participants without diabetes and HbA1c <5.7% (all P > 0.05). […] No differences in the presence of lobar microhemorrhages, subcortical microhemorrhages, cortical infarcts, and lacunar infarcts were observed among the diabetes-HbA1c categories (all P > 0.05) […]. Compared with participants without diabetes and HbA1c <5.7%, those with diabetes and HbA1c ≥7.0% had increased WMH volume (P = 0.016). The WMH volume among participants with diabetes and HbA1c ≥7.0% was also significantly greater than among those with diabetes and HbA1c <7.0% (P = 0.017).”

“Those with diabetes duration ≥10 years were older than those with diabetes duration <10 years (75.9 vs. 75.0 years; P = 0.041) but were similar in terms of race and sex […]. Compared with participants with diabetes duration <10 years, those with diabetes duration ≥10 years has smaller adjusted total brain volume (β −0.13 SDs; 95% CI −0.20, −0.05) and smaller temporal lobe (β −0.14 SDs; 95% CI −0.24, −0.03), parietal lobe (β − 0.11 SDs; 95% CI −0.21, −0.01), and hippocampal (β −0.16 SDs; 95% CI −0.30, −0.02) volumes […]. Participants with diabetes duration ≥10 years also had a 2.44 times increased odds (95% CI 1.46, 4.05) of lacunar infarcts compared with those with diabetes duration <10 years”.

Conclusions
In this community-based population, we found that ARIC-NCS participants with diabetes with HbA1c ≥7.0% have smaller total and regional brain volumes and an increased burden of WMH, but those with prediabetes (HbA1c 5.7 to <6.5%) and diabetes with HbA1c <7.0% have brain volumes and markers of subclinical cerebrovascular disease similar to those without diabetes. Furthermore, among participants with diabetes, those with more-severe disease (as measured by higher HbA1c and longer disease duration) had smaller total and regional brain volumes and an increased burden of cerebrovascular disease compared with those with lower HbA1c and shorter disease duration. However, we found no evidence that associations of diabetes with smaller brain volumes are mediated by cerebrovascular disease.

The findings of this study extend the current literature that suggests that diabetes is strongly associated with brain volume loss (11,2527). Global brain volume loss (11,2527) has been consistently reported, but associations of diabetes with smaller specific brain regions have been less robust (27,28). Similar to prior studies, the current results show that compared with individuals without diabetes, those with diabetes have smaller total brain volume (11,2527) and regional brain volumes, including frontal and occipital lobes, deep gray matter, and the hippocampus (25,27). Furthermore, the current study suggests that greater severity of disease (as measured by HbA1c and diabetes duration) is associated with smaller total and regional brain volumes. […] Mechanisms whereby diabetes may contribute to brain volume loss include accelerated amyloid-β and hyperphosphorylated tau deposition as a result of hyperglycemia (29). Another possible mechanism involves pancreatic amyloid (amylin) infiltration of the brain, which then promotes amyloid-β deposition (29). […] Taken together, […] the current results suggest that diabetes is associated with both lower brain volumes and increased cerebrovascular pathology (WMH and lacunes).”

v. Interventions to increase attendance for diabetic retinopathy screening (Cochrane review).

“The primary objective of the review was to assess the effectiveness of quality improvement (QI) interventions that seek to increase attendance for DRS in people with type 1 and type 2 diabetes.

Secondary objectives were:
To use validated taxonomies of QI intervention strategies and behaviour change techniques (BCTs) to code the description of interventions in the included studies and determine whether interventions that include particular QI strategies or component BCTs are more effective in increasing screening attendance;
To explore heterogeneity in effect size within and between studies to identify potential explanatory factors for variability in effect size;
To explore differential effects in subgroups to provide information on how equity of screening attendance could be improved;
To critically appraise and summarise current evidence on the resource use, costs and cost effectiveness.”

“We included 66 RCTs conducted predominantly (62%) in the USA. Overall we judged the trials to be at low or unclear risk of bias. QI strategies were multifaceted and targeted patients, healthcare professionals or healthcare systems. Fifty-six studies (329,164 participants) compared intervention versus usual care (median duration of follow-up 12 months). Overall, DRS [diabetic retinopathy screening] attendance increased by 12% (risk difference (RD) 0.12, 95% confidence interval (CI) 0.10 to 0.14; low-certainty evidence) compared with usual care, with substantial heterogeneity in effect size. Both DRS-targeted (RD 0.17, 95% CI 0.11 to 0.22) and general QI interventions (RD 0.12, 95% CI 0.09 to 0.15) were effective, particularly where baseline DRS attendance was low. All BCT combinations were associated with significant improvements, particularly in those with poor attendance. We found higher effect estimates in subgroup analyses for the BCTs ‘goal setting (outcome)’ (RD 0.26, 95% CI 0.16 to 0.36) and ‘feedback on outcomes of behaviour’ (RD 0.22, 95% CI 0.15 to 0.29) in interventions targeting patients, and ‘restructuring the social environment’ (RD 0.19, 95% CI 0.12 to 0.26) and ‘credible source’ (RD 0.16, 95% CI 0.08 to 0.24) in interventions targeting healthcare professionals.”

“Ten studies (23,715 participants) compared a more intensive (stepped) intervention versus a less intensive intervention. In these studies DRS attendance increased by 5% (RD 0.05, 95% CI 0.02 to 0.09; moderate-certainty evidence).”

“Overall, we found that there is insufficient evidence to draw robust conclusions about the relative cost effectiveness of the interventions compared to each other or against usual care.”

“The results of this review provide evidence that QI interventions targeting patients, healthcare professionals or the healthcare system are associated with meaningful improvements in DRS attendance compared to usual care. There was no statistically significant difference between interventions specifically aimed at DRS and those which were part of a general QI strategy for improving diabetes care.”

vi. Diabetes in China: Epidemiology and Genetic Risk Factors and Their Clinical Utility in Personalized Medication.

“The incidence of type 2 diabetes (T2D) has rapidly increased over recent decades, and T2D has become a leading public health challenge in China. Compared with European descents, Chinese patients with T2D are diagnosed at a relatively young age and low BMI. A better understanding of the factors contributing to the diabetes epidemic is crucial for determining future prevention and intervention programs. In addition to environmental factors, genetic factors contribute substantially to the development of T2D. To date, more than 100 susceptibility loci for T2D have been identified. Individually, most T2D genetic variants have a small effect size (10–20% increased risk for T2D per risk allele); however, a genetic risk score that combines multiple T2D loci could be used to predict the risk of T2D and to identify individuals who are at a high risk. […] In this article, we review the epidemiological trends and recent progress in the understanding of T2D genetic etiology and further discuss personalized medicine involved in the treatment of T2D.”

“Over the past three decades, the prevalence of diabetes in China has sharply increased. The prevalence of diabetes was reported to be less than 1% in 1980 (2), 5.5% in 2001 (3), 9.7% in 2008 (4), and 10.9% in 2013, according to the latest published nationwide survey (5) […]. The prevalence of diabetes was higher in the senior population, men, urban residents, individuals living in economically developed areas, and overweight and obese individuals. The estimated prevalence of prediabetes in 2013 was 35.7%, which was much higher than the estimate of 15.5% in the 2008 survey. Similarly, the prevalence of prediabetes was higher in the senior population, men, and overweight and obese individuals. However, prediabetes was more prevalent in rural residents than in urban residents. […] the 2013 survey also compared the prevalence of diabetes among different races. The crude prevalence of diabetes was 14.7% in the majority group, i.e., Chinese Han, which was higher than that in most minority ethnic groups, including Tibetan, Zhuang, Uyghur, and Muslim. The crude prevalence of prediabetes was also higher in the Chinese Han ethnic group. The Tibetan participants had the lowest prevalence of diabetes and prediabetes (4.3% and 31.3%).”

“[T]he prevalence of diabetes in young people is relatively high and increasing. The prevalence of diabetes in the 20- to 39-year age-group was 3.2%, according to the 2008 national survey (4), and was 5.9%, according to the 2013 national survey (5). The prevalence of prediabetes also increased from 9.0% in 2008 to 28.8% in 2013 […]. Young people suffering from diabetes have a higher risk of chronic complications, which are the major cause of mortality and morbidity in diabetes. According to a study conducted in Asia (6), patients with young-onset diabetes had higher mean concentrations of HbA1c and LDL cholesterol and a higher prevalence of retinopathy (20% vs. 18%, P = 0.011) than those with late-onset diabetes. In the Chinese, patients with early-onset diabetes had a higher risk of nonfatal cardiovascular disease (7) than did patients with late-onset diabetes (odds ratio [OR] 1.91, 95% CI 1.81–2.02).”

“As approximately 95% of patients with diabetes in China have T2D, the rapid increase in the prevalence of diabetes in China may be attributed to the increasing rates of overweight and obesity and the reduction in physical activity, which is driven by economic development, lifestyle changes, and diet (3,11). According to a series of nationwide surveys conducted by the China Physical Fitness Surveillance Center (12), the prevalence of overweight (BMI ≥23.0 to <27.5 kg/m2) in Chinese adults aged 20–59 years increased from 37.4% in 2000 to 39.2% in 2005, 40.7% in 2010, and 41.2% in 2014, with an estimated increase of 0.27% per year. The prevalence of obesity (BMI ≥27.5 kg/m2) increased from 8.6% in 2000 to 10.3% in 2005, 12.2% in 2010, and 12.9% in 2014, with an estimated increase of 0.32% per year […]. The prevalence of central obesity increased from 13.9% in 2000 to 18.3% in 2005, 22.1% in 2010, and 24.9% in 2014, with an estimated increase of 0.78% per year. Notably, T2D develops at a considerably lower BMI in the Chinese population than that in European populations. […] The relatively high risk of diabetes at a lower BMI could be partially attributed to the tendency toward visceral adiposity in East Asian populations, including the Chinese population (13). Moreover, East Asian populations have been found to have a higher insulin sensitivity with a much lower insulin response than European descent and African populations, implying a lower compensatory β-cell function, which increases the risk of progressing to overt diabetes (14).”

“Over the past two decades, linkage analyses, candidate gene approaches, and large-scale GWAS have successfully identified more than 100 genes that confer susceptibility to T2D among the world’s major ethnic populations […], most of which were discovered in European populations. However, less than 50% of these European-derived loci have been successfully confirmed in East Asian populations. […] there is a need to identify specific genes that are associated with T2D in other ethnic populations. […] Although many genetic loci have been shown to confer susceptibility to T2D, the mechanism by which these loci participate in the pathogenesis of T2D remains unknown. Most T2D loci are located near genes that are related to β-cell function […] most single nucleotide polymorphisms (SNPs) contributing to the T2D risk are located in introns, but whether these SNPs directly modify gene expression or are involved in linkage disequilibrium with unknown causal variants remains to be investigated. Furthermore, the loci discovered thus far collectively account for less than 15% of the overall estimated genetic heritability.”

“The areas under the receiver operating characteristic curves (AUCs) are usually used to assess the discriminative accuracy of an approach. The AUC values range from 0.5 to 1.0, where an AUC of 0.5 represents a lack of discrimination and an AUC of 1 represents perfect discrimination. An AUC ≥0.75 is considered clinically useful. The dominant conventional risk factors, including age, sex, BMI, waist circumference, blood pressure, family history of diabetes, physical activity level, smoking status, and alcohol consumption, can be combined to construct conventional risk factor–based models (CRM). Several studies have compared the predictive capacities of models with and without genetic information. The addition of genetic markers to a CRM could slightly improve the predictive performance. For example, one European study showed that the addition of an 11-SNP GRS to a CRM marginally improved the risk prediction (AUC was 0.74 without and 0.75 with the genetic markers, P < 0.001) in a prospective cohort of 16,000 individuals (37). A meta-analysis (38) consisting of 23 studies investigating the predictive performance of T2D risk models also reported that the AUCs only slightly increased with the addition of genetic information to the CRM (median AUC was increased from 0.78 to 0.79). […] Despite great advances in genetic studies, the clinical utility of genetic information in the prediction, early identification, and prevention of T2D remains in its preliminary stage.”

“An increasing number of studies have highlighted that early nutrition has a persistent effect on the risk of diabetes in later life (40,41). China’s Great Famine of 1959–1962 is considered to be the largest and most severe famine of the 20th century […] Li et al. (43) found that offspring of mothers exposed to the Chinese famine have a 3.9-fold increased risk of diabetes or hyperglycemia as adults. A more recent study (the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors [SPECT-China]) conducted in 2014, among 6,897 adults from Shanghai, Jiangxi, and Zhejiang provinces, had the same conclusion that famine exposure during the fetal period (OR 1.53, 95% CI 1.09–2.14) and childhood (OR 1.82, 95% CI 1.21–2.73) was associated with diabetes (44). These findings indicate that undernutrition during early life increases the risk of hyperglycemia in adulthood and this association is markedly exaggerated when facing overnutrition in later life.”

February 23, 2018 Posted by | Cardiology, Diabetes, Epidemiology, Genetics, Health Economics, Immunology, Medicine, Neurology, Ophthalmology, Pharmacology, Studies | Leave a comment